# gene_set_details

systematic_name: M5866
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NRGGNCAAAGGTCAN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the HNF4A [GeneSymbol=HNF4A] transcription factor binding site V$HNF4_01_B (v7.4 TRANSFAC).


systematic_name: M11244
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNYNYACCTGWVT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TCF8 [GeneSymbol=TCF8] transcription factor binding site V$AREB6_01 (v7.4 TRANSFAC).


systematic_name: M6885
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif WNWCACCTGWNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TCF8 [GeneSymbol=TCF8] transcription factor binding site V$AREB6_02 (v7.4 TRANSFAC).


systematic_name: M10921
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif VNRCACCTGKNC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TCF8 [GeneSymbol=TCF8] transcription factor binding site V$AREB6_03 (v7.4 TRANSFAC).


systematic_name: M8549
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CBGTTTSNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TCF8 [GeneSymbol=TCF8] transcription factor binding site V$AREB6_04 (v7.4 TRANSFAC).


systematic_name: M18233
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M106 CCGNMNNTNACG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M15595
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNTAATTNNCATTANCN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CART1 [GeneSymbol=CART1] transcription factor binding site V$CART1_01 (v7.4 TRANSFAC).


systematic_name: M13313
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif AGCTGTCANNA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TGIF [GeneSymbol=TGIF] transcription factor binding site V$TGIF_01 (v7.4 TRANSFAC).


systematic_name: M7689
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNTGACAGNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MEIS1 [GeneSymbol=MEIS1] transcription factor binding site V$MEIS1_01 (v7.4 TRANSFAC).


systematic_name: M5279
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGACAGKTTTAYGA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MEIS1 [GeneSymbol=MEIS1], HOXA9 [GeneSymbol=HOXA9] transcription factor binding site V$MEIS1AHOXA9_01 (v7.4 TRANSFAC).


systematic_name: M8376
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGACAGTTTTAYGR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MEIS1 [GeneSymbol=MEIS1], HOXA9 [GeneSymbol=HOXA9] transcription factor binding site V$MEIS1BHOXA9_01 (v7.4 TRANSFAC).


systematic_name: M13325
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNWAAAYAAAYANNNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXJ2 [GeneSymbol=FOXJ2] transcription factor binding site V$FOXJ2_01 (v7.4 TRANSFAC).


systematic_name: M15440
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif AYMATAATATTTKN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXJ2 [GeneSymbol=FOXJ2] transcription factor binding site V$FOXJ2_02 (v7.4 TRANSFAC).


systematic_name: M11968
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TWTTTAATTGGTT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NKX6-1 [GeneSymbol=NKX6-1] transcription factor binding site V$NKX61_01 (v7.4 TRANSFAC).


systematic_name: M2651
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M167 CCTNTMAGA in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M4580
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif WCTCAAGTGT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TITF1 [GeneSymbol=TITF1] transcription factor binding site V$TITF1_Q3 (v7.4 TRANSFAC).


systematic_name: M6490
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GHNNTAATGACM in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the IPF1 [GeneSymbol=IPF1] transcription factor binding site V$IPF1_Q4 (v7.4 TRANSFAC).


systematic_name: M11587
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNTAATTAGCNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the VSX1 [GeneSymbol=VSX1] transcription factor binding site V$CHX10_01 (v7.4 TRANSFAC).


systematic_name: M14782
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GGGKNARNRRGGWSA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the VDR [GeneSymbol=VDR] transcription factor binding site V$VDR_Q3 (v7.4 TRANSFAC).


systematic_name: M17319
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif DNNGGRGGGWWNNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SPZ1 [GeneSymbol=SPZ1] transcription factor binding site V$SPZ1_01 (v7.4 TRANSFAC).


systematic_name: M10936
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M81 CGGAARNGGCNG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M16805
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif AGWACATNWTGTTCT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the AR [GeneSymbol=AR] transcription factor binding site V$AR_Q2 (v7.4 TRANSFAC).


systematic_name: M13482
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif KGGGTGGTC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ZIC1 [GeneSymbol=ZIC1] transcription factor binding site V$ZIC1_01 (v7.4 TRANSFAC).


systematic_name: M7797
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif KGGGTGGTC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ZIC2 [GeneSymbol=ZIC2] transcription factor binding site V$ZIC2_01 (v7.4 TRANSFAC).


systematic_name: M7622
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NGGGKGGTC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ZIC3 [GeneSymbol=ZIC3] transcription factor binding site V$ZIC3_01 (v7.4 TRANSFAC).


systematic_name: M16345
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NWATAAGTATWT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NKX3-1 [GeneSymbol=NKX3-1] transcription factor binding site V$NKX3A_01 (v7.4 TRANSFAC).


systematic_name: M12258
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TNSGAAWNCGAAANTNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the IRF7 [GeneSymbol=IRF7] transcription factor binding site V$IRF7_01 (v7.4 TRANSFAC).


systematic_name: M8826
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNCAMAACACRNA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FALZ [GeneSymbol=FALZ] transcription factor binding site V$FAC1_01 (v7.4 TRANSFAC).


systematic_name: M17883
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NAWTTCYNGGAANYN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the STAT5A [GeneSymbol=STAT5A] transcription factor binding site V$STAT5A_01 (v7.4 TRANSFAC).


systematic_name: M6144
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NAWTTCYNGGAAWTN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the STAT5B [GeneSymbol=STAT5B] transcription factor binding site V$STAT5B_01 (v7.4 TRANSFAC).


systematic_name: M18386
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TTCCNRGAANNNNNNTTCCNNGRR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the STAT5A [GeneSymbol=STAT5A] transcription factor binding site V$STAT5A_02 (v7.4 TRANSFAC).


systematic_name: M2688
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M100 CRGAARNNNNCGA in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M13052
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNGATWANN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the GATA6 [GeneSymbol=GATA6] transcription factor binding site V$GATA6_01 (v7.4 TRANSFAC).


systematic_name: M3720
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif ATGMATWWATTCAT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the POU3F2 [GeneSymbol=POU3F2] transcription factor binding site V$POU3F2_01 (v7.4 TRANSFAC).


systematic_name: M14960
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TTATGYTAAT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the POU3F2 [GeneSymbol=POU3F2] transcription factor binding site V$POU3F2_02 (v7.4 TRANSFAC).


systematic_name: M6135
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GCATAAWTTAT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the POU6F1 [GeneSymbol=POU6F1] transcription factor binding site V$POU6F1_01 (v7.4 TRANSFAC).


systematic_name: M5320
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CGTACGTGCNGB in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the HIF1A [GeneSymbol=HIF1A] transcription factor binding site V$HIF1_Q5 (v7.4 TRANSFAC).


systematic_name: M4134
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CAGTGGG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the KLF12 [GeneSymbol=KLF12] transcription factor binding site V$AP2REP_01 (v7.4 TRANSFAC).


systematic_name: M18732
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GCCNNNRGS in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TFAP2A [GeneSymbol=TFAP2A] transcription factor binding site V$AP2ALPHA_01 (v7.4 TRANSFAC).


systematic_name: M16396
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GCCYNNGGS in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TFAP2C [GeneSymbol=TFAP2C] transcription factor binding site V$AP2GAMMA_01 (v7.4 TRANSFAC).


systematic_name: M6994
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TATAAATW in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TBP [GeneSymbol=TBP] transcription factor binding site V$TBP_01 (v7.4 TRANSFAC).


systematic_name: M6054
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M171 CTCNANGTGNY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M11461
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RWAAACAANNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MLLT7 [GeneSymbol=MLLT7] transcription factor binding site V$FOXO4_01 (v7.4 TRANSFAC).


systematic_name: M11512
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NRWAAACAAN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXO1A [GeneSymbol=FOXO1A] transcription factor binding site V$FOXO1_01 (v7.4 TRANSFAC).


systematic_name: M4774
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GNNTTGTTTACNTT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXO1A [GeneSymbol=FOXO1A] transcription factor binding site V$FOXO1_02 (v7.4 TRANSFAC).


systematic_name: M16417
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNGTTGTTTACNTN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MLLT7 [GeneSymbol=MLLT7] transcription factor binding site V$FOXO4_02 (v7.4 TRANSFAC).


systematic_name: M19851
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TNNTTGTTTACNTW in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXO3A [GeneSymbol=FOXO3A] transcription factor binding site V$FOXO3_01 (v7.4 TRANSFAC).


systematic_name: M19327
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GATTTAACATAA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CDC5L [GeneSymbol=CDC5L] transcription factor binding site V$CDC5_01 (v7.4 TRANSFAC).


systematic_name: M16670
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GGTACANNRTGTTCT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the AR [GeneSymbol=AR] transcription factor binding site V$AR_01 (v7.4 TRANSFAC).


systematic_name: M16280
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif WNTAATCCCAR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PITX2 [GeneSymbol=PITX2] transcription factor binding site V$PITX2_Q2 (v7.4 TRANSFAC).


systematic_name: M5987
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGACGTGG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ATF6 [GeneSymbol=ATF6] transcription factor binding site V$ATF6_01 (v7.4 TRANSFAC).


systematic_name: M9896
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNGTAAKTNG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TLX2 [GeneSymbol=TLX2] transcription factor binding site V$NCX_01 (v7.4 TRANSFAC).


systematic_name: M9769
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M101 CTGCAGY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M14350
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TTAAGTRSTT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NKX2-2 [GeneSymbol=NKX2-2] transcription factor binding site V$NKX22_01 (v7.4 TRANSFAC).


systematic_name: M17779
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNAAASNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PAX2 [GeneSymbol=PAX2] transcription factor binding site V$PAX2_02 (v7.4 TRANSFAC).


systematic_name: M12379
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NWADTAAWTANN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NKX6-2 [GeneSymbol=NKX6-2] transcription factor binding site V$NKX62_Q2 (v7.4 TRANSFAC).


systematic_name: M13237
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif SRTGAGTCANC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the BACH2 [GeneSymbol=BACH2] transcription factor binding site V$BACH2_01 (v7.4 TRANSFAC).


systematic_name: M4453
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NSGGGGGGGGMCN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$MAZR_01 (v7.4 TRANSFAC).


systematic_name: M17769
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CANTTCCS in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the STAT1 [GeneSymbol=STAT1] transcription factor binding site V$STAT1_02 (v7.4 TRANSFAC).


systematic_name: M8720
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NAWTTCYN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the STAT5A [GeneSymbol=STAT5A] transcription factor binding site V$STAT5A_03 (v7.4 TRANSFAC).


systematic_name: M2490
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NAWTTCCN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the STAT6 [GeneSymbol=STAT6] transcription factor binding site V$STAT6_01 (v7.4 TRANSFAC).


systematic_name: M6969
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNSATGAGTCATGNT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the BACH1 [GeneSymbol=BACH1] transcription factor binding site V$BACH1_01 (v7.4 TRANSFAC).


systematic_name: M2146
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNTTTCCN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the STAT1 [GeneSymbol=STAT1] transcription factor binding site V$STAT1_03 (v7.4 TRANSFAC).


systematic_name: M3285
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M153 CTGRYYYNATT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M3263
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNTTCCN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the STAT3 [GeneSymbol=STAT3] transcription factor binding site V$STAT3_02 (v7.4 TRANSFAC).


systematic_name: M3339
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif SNWTTCNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the STAT4 [GeneSymbol=STAT4] transcription factor binding site V$STAT4_01 (v7.4 TRANSFAC).


systematic_name: M4372
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNTTCYN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the STAT5A [GeneSymbol=STAT5A] transcription factor binding site V$STAT5A_04 (v7.4 TRANSFAC).


systematic_name: M7994
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNYTTCCY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the STAT6 [GeneSymbol=STAT6] transcription factor binding site V$STAT6_02 (v7.4 TRANSFAC).


systematic_name: M11495
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif AATTAATTAA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the LHX3 [GeneSymbol=LHX3] transcription factor binding site V$LHX3_01 (v7.4 TRANSFAC).


systematic_name: M2489
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNTNAAGGTCANN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ESRRA [GeneSymbol=ESRRA] transcription factor binding site V$ERR1_Q2 (v7.4 TRANSFAC).


systematic_name: M17278
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNWGRGGTCAAAGGTCANNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PPARG [GeneSymbol=PPARG] transcription factor binding site V$PPARG_01 (v7.4 TRANSFAC).


systematic_name: M13967
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CBCTGACGTCANCS in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ATF3 [GeneSymbol=ATF3] transcription factor binding site V$ATF3_Q6 (v7.4 TRANSFAC).


systematic_name: M14402
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CVTGACGYMABG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ATF4 [GeneSymbol=ATF4] transcription factor binding site V$ATF4_Q2 (v7.4 TRANSFAC).


systematic_name: M15647
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M82 CTGYNNCTYTAA in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M10220
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNTGAGTCAKCN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the JUN [GeneSymbol=JUN] transcription factor binding site V$AP1_01 (v7.4 TRANSFAC).


systematic_name: M3739
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNRGGTCATWGGGGTSANG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PPARA [GeneSymbol=PPARA] transcription factor binding site V$PPARA_02 (v7.4 TRANSFAC).


systematic_name: M3011
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NTCAAGKTCAAGKTCANN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NR6A1 [GeneSymbol=NR6A1] transcription factor binding site V$GNCF_01 (v7.4 TRANSFAC).


systematic_name: M1607
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif YRNCAGGAAGYRNSTBDS in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ELF2 [GeneSymbol=ELF2] transcription factor binding site V$NERF_Q2 (v7.4 TRANSFAC).


systematic_name: M2120
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNAACATCTGGA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ZNF238 [GeneSymbol=ZNF238] transcription factor binding site V$RP58_01 (v7.4 TRANSFAC).


systematic_name: M14002
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNWWWWNGMCACGTCATYNYWNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$HTF_01 (v7.4 TRANSFAC).


systematic_name: M9795
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNNNRTCACGTGAYNNNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ARNT [GeneSymbol=ARNT] transcription factor binding site V$ARNT_02 (v7.4 TRANSFAC).


systematic_name: M17944
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNNNNNCACGTGNNNNNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MYC [GeneSymbol=MYC], MAX [GeneSymbol=MAX] transcription factor binding site V$MYCMAX_03 (v7.4 TRANSFAC).


systematic_name: M14351
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif ATTAAYTRCAC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ZHX2 [GeneSymbol=ZHX2] transcription factor binding site V$AFP1_Q6 (v7.4 TRANSFAC).


systematic_name: M2518
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CCTGAGAATAATC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ALX4 [GeneSymbol=ALX4] transcription factor binding site V$ALX4_01 (v7.4 TRANSFAC).


systematic_name: M3684
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M29 CTTTAAR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M8474
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif MATTKCNTMAYY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CEBPD [GeneSymbol=CEBPD] transcription factor binding site V$CEBPDELTA_Q6 (v7.4 TRANSFAC).


systematic_name: M3741
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CTBATTTCARAAW in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CEBPG [GeneSymbol=CEBPG] transcription factor binding site V$CEBPGAMMA_Q6 (v7.4 TRANSFAC).


systematic_name: M7023
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif YNNNTAATCYCMN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CRX [GeneSymbol=CRX] transcription factor binding site V$CRX_Q4 (v7.4 TRANSFAC).


systematic_name: M15349
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif AGCAHAC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the DBP [GeneSymbol=DBP] transcription factor binding site V$DBP_Q6 (v7.4 TRANSFAC).


systematic_name: M1181
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif MGTTACYAGGCAAM in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the RFX1 [GeneSymbol=RFX1] transcription factor binding site V$EFC_Q6 (v7.4 TRANSFAC).


systematic_name: M4468
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif ARATKGAST in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXM1 [GeneSymbol=FOXM1] transcription factor binding site V$FOXM1_01 (v7.4 TRANSFAC).


systematic_name: M9731
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CARGKTSAWTRACC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NR1H4 [GeneSymbol=NR1H4] transcription factor binding site V$FXR_Q3 (v7.4 TRANSFAC).


systematic_name: M15522
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif AGATADMAGGGA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the GATA4 [GeneSymbol=GATA4] transcription factor binding site V$GATA4_Q3 (v7.4 TRANSFAC).


systematic_name: M955
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CNNRCCCGCATD in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the GCM1 [GeneSymbol=GCM1] transcription factor binding site V$GCM_Q2 (v7.4 TRANSFAC).


systematic_name: M18844
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif VTGAACTTTGMMB in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the HNF4A [GeneSymbol=HNF4A] transcription factor binding site V$HNF4ALPHA_Q6 (v7.4 TRANSFAC).


systematic_name: M13977
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M34 CYTAGCAAY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M8172
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif HWAAATCAATAW in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ONECUT1 [GeneSymbol=ONECUT1] transcription factor binding site V$HNF6_Q6 (v7.4 TRANSFAC).


systematic_name: M16178
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif AWAATTRG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the HOXA4 [GeneSymbol=HOXA4] transcription factor binding site V$HOXA4_Q2 (v7.4 TRANSFAC).


systematic_name: M7806
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TTCCMGARGYTTC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$HSF_Q6 (v7.4 TRANSFAC).


systematic_name: M2998
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CAGCTGS in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the UBP1 [GeneSymbol=UBP1] transcription factor binding site V$LBP1_Q6 (v7.4 TRANSFAC).


systematic_name: M10767
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GGGSTCWR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ITGAL [GeneSymbol=ITGAL] transcription factor binding site V$LFA1_Q6 (v7.4 TRANSFAC).


systematic_name: M14687
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGGGGTYACTNNCGGTCA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NR1H3 [GeneSymbol=NR1H3] transcription factor binding site V$LXR_Q3 (v7.4 TRANSFAC).


systematic_name: M14583
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TRGRRGGAAGTKKSST in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MAF [GeneSymbol=MAF] transcription factor binding site V$MAF_Q6 (v7.4 TRANSFAC).


systematic_name: M11022
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GGGGAGGG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MAZ [GeneSymbol=MAZ] transcription factor binding site V$MAZ_Q6 (v7.4 TRANSFAC).


systematic_name: M2463
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TBTGCACHCGGCCC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MTF1 [GeneSymbol=MTF1] transcription factor binding site V$MTF1_Q4 (v7.4 TRANSFAC).


systematic_name: M3265
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CGGCCATCT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$NFMUE1_Q6 (v7.4 TRANSFAC).


systematic_name: M10627
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M137 GAANYNYGACNY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M2907
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CGCATGCGCR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NRF1 [GeneSymbol=NRF1] transcription factor binding site V$NRF1_Q6 (v7.4 TRANSFAC).


systematic_name: M9287
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif ACWTCCK in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ETV4 [GeneSymbol=ETV4] transcription factor binding site V$PEA3_Q6 (v7.4 TRANSFAC).


systematic_name: M15389
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GRGAAAMBBWCAGS in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PTF1A [GeneSymbol=PTF1A] transcription factor binding site V$PTF1BETA_Q6 (v7.4 TRANSFAC).


systematic_name: M14376
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif WGAGGAAG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SPI1 [GeneSymbol=SPI1] transcription factor binding site V$PU1_Q6 (v7.4 TRANSFAC).


systematic_name: M10836
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif ASMCTTGGGSRGGG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SP3 [GeneSymbol=SP3] transcription factor binding site V$SP3_Q3 (v7.4 TRANSFAC).


systematic_name: M4088
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GKCRGKTT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TCF1 [GeneSymbol=TCF1] transcription factor binding site V$TCF1P_Q6 (v7.4 TRANSFAC).


systematic_name: M1224
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif SCTTTGAW in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TCF4 [GeneSymbol=TCF4] transcription factor binding site V$TCF4_Q5 (v7.4 TRANSFAC).


systematic_name: M19671
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif ATGTTWAYATAA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TEF [GeneSymbol=TEF] transcription factor binding site V$TEF_Q6 (v7.4 TRANSFAC).


systematic_name: M5155
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif YTACTTCCTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ETV7 [GeneSymbol=ETV7] transcription factor binding site V$TEL2_Q6 (v7.4 TRANSFAC).


systematic_name: M8797
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CAGCCAATGAG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PCBP1 [GeneSymbol=PCBP1] transcription factor binding site V$ALPHACP1_01 (v7.4 TRANSFAC).


systematic_name: M16653
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M148 GATGKMRGCG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M498
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TCYMMATT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$AP3_Q6 (v7.4 TRANSFAC).


systematic_name: M12826
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CYYTGACGTCA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ATF1 [GeneSymbol=ATF1] transcription factor binding site V$ATF1_Q6 (v7.4 TRANSFAC).


systematic_name: M15183
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RRCAGGTGNCV in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TCF3 [GeneSymbol=TCF3] transcription factor binding site V$E12_Q6 (v7.4 TRANSFAC).


systematic_name: M13493
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif SYTACGTCAC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the E4F1 [GeneSymbol=E4F1] transcription factor binding site V$E4F1_Q6 (v7.4 TRANSFAC).


systematic_name: M17024
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GVGGMGG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$ETF_Q6 (v7.4 TRANSFAC).


systematic_name: M18576
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RCCWGCTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TCF12 [GeneSymbol=TCF12] transcription factor binding site V$HEB_Q6 (v7.4 TRANSFAC).


systematic_name: M2727
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RAARTGAAACTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the IRF8 [GeneSymbol=IRF8] transcription factor binding site V$ICSBP_Q6 (v7.4 TRANSFAC).


systematic_name: M6325
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGTCTGTCT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SMAD3 [GeneSymbol=SMAD3] transcription factor binding site V$SMAD3_Q6 (v7.4 TRANSFAC).


systematic_name: M551
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GRRATG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$TEF1_Q6 (v7.4 TRANSFAC).


systematic_name: M7338
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RGAGGKAGG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the GTF2A1 [GeneSymbol=GTF2A1], GTF2A2 [GeneSymbol=GTF2A2] transcription factor binding site V$TFIII_Q6 (v7.4 TRANSFAC).


systematic_name: M1779
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M95 GCCNNNWTAAR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M8585
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TMTRWRAGGRSS in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the GTF2A1 [GeneSymbol=GTF2A1], GTF2A2 [GeneSymbol=GTF2A2] transcription factor binding site V$TFIIA_Q6 (v7.4 TRANSFAC).


systematic_name: M10411
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RGCAGSTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MYOG [GeneSymbol=MYOG] transcription factor binding site V$MYOGENIN_Q6 (v7.4 TRANSFAC).


systematic_name: M1793
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GSGCGCGR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ZFP161 [GeneSymbol=ZFP161] transcription factor binding site V$ZF5_01 (v7.4 TRANSFAC).


systematic_name: M3139
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNTNNNGNGTGANN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PAX8 [GeneSymbol=PAX8] transcription factor binding site V$PAX8_01 (v7.4 TRANSFAC).


systematic_name: M2209
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GRGGSTGGG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$CACBINDINGPROTEIN_Q6 (v7.4 TRANSFAC).


systematic_name: M6446
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CANCCNNWGGGTGDGG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$CACCCBINDINGFACTOR_Q6 (v7.4 TRANSFAC).


systematic_name: M4770
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGTGGTTW in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CBFA2T2 [GeneSymbol=CBFA2T2], CBFA2T3 [GeneSymbol=CBFA2T3] transcription factor binding site V$COREBINDINGFACTOR_Q6 (v7.4 TRANSFAC).


systematic_name: M10428
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TRTTTGYTYWN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXA1 [GeneSymbol=FOXA1] transcription factor binding site V$HNF3ALPHA_Q6 (v7.4 TRANSFAC).


systematic_name: M13584
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif AATWTTCAACAG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$HP1SITEFACTOR_Q6 (v7.4 TRANSFAC).


systematic_name: M17508
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CASGYG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$USF2_Q6 (v7.4 TRANSFAC).


systematic_name: M401
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M48 GCGNNANTTCC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M8812
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGRCCTTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SF1 [GeneSymbol=SF1] transcription factor binding site V$SF1_Q6 (v7.4 TRANSFAC).


systematic_name: M8062
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif ANANTTTTATKRCC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CDX2 [GeneSymbol=CDX2] transcription factor binding site V$CDX2_Q5 (v7.4 TRANSFAC).


systematic_name: M17644
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif ACCACANM in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the RUNX2 [GeneSymbol=RUNX2] transcription factor binding site V$OSF2_Q6 (v7.4 TRANSFAC).


systematic_name: M18670
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GKSRKKCAGMCANCY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SMAD4 [GeneSymbol=SMAD4] transcription factor binding site V$SMAD4_Q6 (v7.4 TRANSFAC).


systematic_name: M3799
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif SAAAAANNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ZNF384 [GeneSymbol=ZNF384] transcription factor binding site V$CIZ_01 (v7.4 TRANSFAC).


systematic_name: M17426
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M164 GCGSCMNTTT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1341
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif AWKTGTTTGTTTA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXJ1 [GeneSymbol=FOXJ1] transcription factor binding site V$HFH4_01 (v7.4 TRANSFAC).


systematic_name: M3902
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif ATGAATAAWT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the POU1F1 [GeneSymbol=POU1F1] transcription factor binding site V$POU1F1_Q6 (v7.4 TRANSFAC).


systematic_name: M14944
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif SWWCAAAGGG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the LEF1 [GeneSymbol=LEF1], TCF1 [GeneSymbol=TCF1] transcription factor binding site V$LEF1_Q6 (v7.4 TRANSFAC).


systematic_name: M9902
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RNWMBAGGAART in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ELF1 [GeneSymbol=ELF1] transcription factor binding site V$ELF1_Q6 (v7.4 TRANSFAC).


systematic_name: M13173
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TTCACTT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the IRF1 [GeneSymbol=IRF1] transcription factor binding site V$IRF1_Q6 (v7.4 TRANSFAC).


systematic_name: M19265
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CACSCCA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SREBF1 [GeneSymbol=SREBF1] transcription factor binding site V$SREBP1_Q6 (v7.4 TRANSFAC).


systematic_name: M19147
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GGAAAWT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the HMGA1 [GeneSymbol=HMGA1] transcription factor binding site V$HMGIY_Q6 (v7.4 TRANSFAC).


systematic_name: M6002
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGTGGT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the RUNX1 [GeneSymbol=RUNX1] transcription factor binding site V$AML1_Q6 (v7.4 TRANSFAC).


systematic_name: M16079
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RGRCAWGNCY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TP53 [GeneSymbol=TP53] transcription factor binding site V$P53_DECAMER_Q2 (v7.4 TRANSFAC).


systematic_name: M4644
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RGGNCAAAGGTCA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NR2F2 [GeneSymbol=NR2F2] transcription factor binding site V$DR1_Q3 (v7.4 TRANSFAC).


systematic_name: M8942
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M78 GCTNWTTGK in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M13889
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGACCTTTGNCCY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PPARA [GeneSymbol=PPARA] transcription factor binding site V$PPAR_DR1_Q2 (v7.4 TRANSFAC).


systematic_name: M13332
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGAMCTTTGNCCN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the HNF4A [GeneSymbol=HNF4A] transcription factor binding site V$HNF4_DR1_Q3 (v7.4 TRANSFAC).


systematic_name: M18594
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGACCTTTGACCC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PITX2 [GeneSymbol=PITX2] transcription factor binding site V$COUP_DR1_Q6 (v7.4 TRANSFAC).


systematic_name: M5331
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGACCGNNAGTRACCC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NR1H3 [GeneSymbol=NR1H3] transcription factor binding site V$LXR_DR4_Q3 (v7.4 TRANSFAC).


systematic_name: M1013
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GGGTBAATRACCY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the RXRA [GeneSymbol=RXRA] transcription factor binding site V$FXR_IR1_Q6 (v7.4 TRANSFAC).


systematic_name: M12818
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNGKNTGTGGTTWNC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the RUNX1 [GeneSymbol=RUNX1] transcription factor binding site V$AML_Q6 (v7.4 TRANSFAC).


systematic_name: M3109
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNTKNNGNAAN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CEBPA [GeneSymbol=CEBPA] transcription factor binding site V$CEBP_Q3 (v7.4 TRANSFAC).


systematic_name: M18230
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif ANNCACTTCCTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ETS1 [GeneSymbol=ETS1] transcription factor binding site V$ETS_Q4 (v7.4 TRANSFAC).


systematic_name: M14066
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif BNCRSTTTCANTTYY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the IRF1 [GeneSymbol=IRF1] transcription factor binding site V$IRF_Q6 (v7.4 TRANSFAC).


systematic_name: M14466
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNGNCAGTTN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MYB [GeneSymbol=MYB] transcription factor binding site V$MYB_Q3 (v7.4 TRANSFAC).


systematic_name: M12891
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M21 GGAANCGGAANY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M2549
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNNKGGRAANTCCCN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$NFKB_Q6_01 (v7.4 TRANSFAC).


systematic_name: M2409
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNNRRCCAATSR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$NFY_Q6_01 (v7.4 TRANSFAC).


systematic_name: M2814
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif VNNVTCACCCYA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$SREBP_Q3 (v7.4 TRANSFAC).


systematic_name: M3437
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNNNTTCTKGGA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$STAT_Q6 (v7.4 TRANSFAC).


systematic_name: M17378
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NTNGCGTGNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the AHR [GeneSymbol=AHR] transcription factor binding site V$AHR_Q5 (v7.4 TRANSFAC).


systematic_name: M16459
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif WGATARN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the GATA1 [GeneSymbol=GATA1] transcription factor binding site V$GATA_Q6 (v7.4 TRANSFAC).


systematic_name: M11442
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif WRGTTAATNATTAACNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TCF1 [GeneSymbol=TCF1] transcription factor binding site V$HNF1_Q6 (v7.4 TRANSFAC).


systematic_name: M17512
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NWRARYAAAYANN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXA1 [GeneSymbol=FOXA1] transcription factor binding site V$HNF3_Q6 (v7.4 TRANSFAC).


systematic_name: M1903
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif AGACNBCNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SMAD1 [GeneSymbol=SMAD1] transcription factor binding site V$SMAD_Q6 (v7.4 TRANSFAC).


systematic_name: M11698
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GCCATNTTN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the YY1 [GeneSymbol=YY1] transcription factor binding site V$YY1_Q6 (v7.4 TRANSFAC).


systematic_name: M11597
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M74 GGAMTNNNNNTCCY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M6331
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNNCAAGNRNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TITF1 [GeneSymbol=TITF1] transcription factor binding site V$TTF1_Q6 (v7.4 TRANSFAC).


systematic_name: M2211
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TNATTTGCATN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$OCT_Q6 (v7.4 TRANSFAC).


systematic_name: M8895
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NRCCACGTGASN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$USF_Q6_01 (v7.4 TRANSFAC).


systematic_name: M14011
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GNNKACGTGCGGNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the HIF1A [GeneSymbol=HIF1A] transcription factor binding site V$HIF1_Q3 (v7.4 TRANSFAC).


systematic_name: M17805
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CACGTGS in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MYC [GeneSymbol=MYC] transcription factor binding site V$MYC_Q2 (v7.4 TRANSFAC).


systematic_name: M11469
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GSCCSCRGGCNRNRNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the GTF3A [GeneSymbol=GTF3A] transcription factor binding site V$AP2_Q3 (v7.4 TRANSFAC).


systematic_name: M14786
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CGTCAN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CREB1 [GeneSymbol=CREB1] transcription factor binding site V$CREB_Q3 (v7.4 TRANSFAC).


systematic_name: M15591
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NMTTCATAAWTATWNMNA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the POU1F1 [GeneSymbol=POU1F1] transcription factor binding site V$PIT1_Q6 (v7.4 TRANSFAC).


systematic_name: M4155
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GGCGSG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the E2F [GeneSymbol=E2F], TFDP1 [GeneSymbol=TFDP1] transcription factor binding site V$E2F_Q2 (v7.4 TRANSFAC).


systematic_name: M17596
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NCACCTGYYNCNKN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TCF3 [GeneSymbol=TCF3] transcription factor binding site V$E2A_Q2 (v7.4 TRANSFAC).


systematic_name: M13187
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M163 GGARNTKYCCA in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M3572
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TCAAAG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the LEF1 [GeneSymbol=LEF1], TCF1 [GeneSymbol=TCF1] transcription factor binding site V$LEF1_Q2 (v7.4 TRANSFAC).


systematic_name: M12915
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NTGGNNNNNNGCCAANN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NF1 [GeneSymbol=NF1] transcription factor binding site V$NF1_Q6_01 (v7.4 TRANSFAC).


systematic_name: M2459
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GTGGGSGCRRS in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the EGR1 [GeneSymbol=EGR1], EGR2 [GeneSymbol=EGR2], EGR3 [GeneSymbol=EGR3] transcription factor binding site V$EGR_Q6 (v7.4 TRANSFAC).


systematic_name: M9426
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CTGGAACTMAC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PAX2 [GeneSymbol=PAX2] transcription factor binding site V$PAX_Q6 (v7.4 TRANSFAC).


systematic_name: M1643
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif KATTGTTTRTTTW in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXF2 [GeneSymbol=FOXF2] transcription factor binding site V$FOX_Q2 (v7.4 TRANSFAC).


systematic_name: M5479
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif SCCAWATAWGGMNMNNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SRF [GeneSymbol=SRF] transcription factor binding site V$SRF_Q4 (v7.4 TRANSFAC).


systematic_name: M14141
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NTGCTGAGTCAKN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NFE2L2 [GeneSymbol=NFE2L2] transcription factor binding site V$NRF2_Q4 (v7.4 TRANSFAC).


systematic_name: M6830
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NTTRCNNAANNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CEBPA [GeneSymbol=CEBPA] transcription factor binding site V$CEBP_Q2_01 (v7.4 TRANSFAC).


systematic_name: M16722
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NAACNGNCN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MYB [GeneSymbol=MYB] transcription factor binding site V$MYB_Q5_01 (v7.4 TRANSFAC).


systematic_name: M13780
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M159 GGCKCATGS in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M16207
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif SNNNCCNCAGGCN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the GTF3A [GeneSymbol=GTF3A] transcription factor binding site V$AP2_Q6_01 (v7.4 TRANSFAC).


systematic_name: M13982
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNTKACGTCANNNS in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CREB1 [GeneSymbol=CREB1] transcription factor binding site V$CREB_Q2_01 (v7.4 TRANSFAC).


systematic_name: M3410
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CNNTGACGTMA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CREB1 [GeneSymbol=CREB1] transcription factor binding site V$CREB_Q4_01 (v7.4 TRANSFAC).


systematic_name: M3647
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNTGTYCT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NR3C1 [GeneSymbol=NR3C1] transcription factor binding site V$GR_Q6_01 (v7.4 TRANSFAC).


systematic_name: M11934
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CCAWATAWGGMNMNG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SRF [GeneSymbol=SRF] transcription factor binding site V$SRF_Q5_01 (v7.4 TRANSFAC).


systematic_name: M7477
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGACTCANNSKN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the JUN [GeneSymbol=JUN] transcription factor binding site V$AP1_Q2_01 (v7.4 TRANSFAC).


systematic_name: M2054
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NTGACTCAN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the JUN [GeneSymbol=JUN] transcription factor binding site V$AP1_Q6_01 (v7.4 TRANSFAC).


systematic_name: M11715
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M88 GGCNKCCATNK in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M12460
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TGAGTCAN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the JUN [GeneSymbol=JUN] transcription factor binding site V$AP1_Q4_01 (v7.4 TRANSFAC).


systematic_name: M2685
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RNCAGCTGC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TFAP4 [GeneSymbol=TFAP4] transcription factor binding site V$AP4_Q6_01 (v7.4 TRANSFAC).


systematic_name: M4998
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CNGNRNCAGGTGNNGNAN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MYOD1 [GeneSymbol=MYOD1] transcription factor binding site V$MYOD_Q6_01 (v7.4 TRANSFAC).


systematic_name: M9638
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif TNATTTGCATW in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the POU2F1 [GeneSymbol=POU2F1] transcription factor binding site V$OCT1_Q5_01 (v7.4 TRANSFAC).


systematic_name: M9557
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GGGGCGGGGC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SP1 [GeneSymbol=SP1] transcription factor binding site V$SP1_Q6_01 (v7.4 TRANSFAC).


systematic_name: M9300
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNGGGGCGGGGNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SP1 [GeneSymbol=SP1] transcription factor binding site V$SP1_Q4_01 (v7.4 TRANSFAC).


systematic_name: M11791
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CCCCGCCCCN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SP1 [GeneSymbol=SP1] transcription factor binding site V$SP1_Q2_01 (v7.4 TRANSFAC).


systematic_name: M8280
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NWGGAAANWN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NFAT [GeneSymbol=NFAT], NFATC [GeneSymbol=NFATC] transcription factor binding site V$NFAT_Q4_01 (v7.4 TRANSFAC).


systematic_name: M15570
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M123 GGCNNMSMYNTTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M15929
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RGCTATWTTTAR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$MEF2_Q6_01 (v7.4 TRANSFAC).


systematic_name: M560
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif GCTGGNTNGNNCYNG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TFCP2 [GeneSymbol=TFCP2] transcription factor binding site V$CP2_02 (v7.4 TRANSFAC).


systematic_name: M3586
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNGNRRGNACANNGTGTTCTNNNNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the AR [GeneSymbol=AR] transcription factor binding site V$AR_02 (v7.4 TRANSFAC).


systematic_name: M19455
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNNNNGGNACRNNNTGTTCTNNNNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PGR [GeneSymbol=PGR] transcription factor binding site V$PR_01 (v7.4 TRANSFAC).


systematic_name: M8603
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNNNNNGKACNNNNTGTTCTNNNNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NR3C1 [GeneSymbol=NR3C1] transcription factor binding site V$GR_01 (v7.4 TRANSFAC).


systematic_name: M2274
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNNNNRGNACRNNGTGTTCTNNNNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the AR [GeneSymbol=AR] transcription factor binding site V$AR_03 (v7.4 TRANSFAC).


systematic_name: M6097
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NNNNNNRGNACNNKNTGTTCTNNNNNN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PGR [GeneSymbol=PGR] transcription factor binding site V$PR_02 (v7.4 TRANSFAC).


systematic_name: M17968
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NAGGTCANNNY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ESR1 [GeneSymbol=ESR1] transcription factor binding site V$ER_Q6_02 (v7.4 TRANSFAC).


systematic_name: M19331
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif NWNAGRACAN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NR3C1 [GeneSymbol=NR3C1] transcription factor binding site V$PR_Q2 (v7.4 TRANSFAC).


systematic_name: M4631
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M118 GGCNRNWCTTYS in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M217
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif CNSNNTGAACCN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the VDR [GeneSymbol=VDR] transcription factor binding site V$VDR_Q6 (v7.4 TRANSFAC).


systematic_name: M19962
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif WGAGCANRN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the AR [GeneSymbol=AR] transcription factor binding site V$AR_Q6 (v7.4 TRANSFAC).


systematic_name: M4061
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif MNTGWCCTN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$T3R_Q6 (v7.4 TRANSFAC).


systematic_name: M4153
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RRGGTYANTRNM in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NR1H4 [GeneSymbol=NR1H4] transcription factor binding site V$PXR_Q2 (v7.4 TRANSFAC).


systematic_name: M4321
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif YGAMCTNNASTRACCYN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the RXRB [GeneSymbol=RXRB] transcription factor binding site V$DR4_Q2 (v7.4 TRANSFAC).


systematic_name: M1631
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif RRTGNMCYTNNTGAMCCNYNT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the VDR [GeneSymbol=VDR] transcription factor binding site V$DR3_Q4 (v7.4 TRANSFAC).


systematic_name: M8634
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the motif AARGTCCAN in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the HNF4A [GeneSymbol=HNF4A] transcription factor binding site V$HNF4_Q6 (v7.4 TRANSFAC).


systematic_name: M1064
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M119 GGGNRMNNYCAT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M9645
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M31 GGGYGTGNY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M2826
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M19 GKCGCNNNNNNNTGAYG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M8013
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M98 GTCNYYATGR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M6628
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M91 GTGGGTGK in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M7220
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M43 GTTGNYNNRGNAAC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M7386
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M89 GTTNYYNNGGTNA in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M8756
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M37 GTTRYCATRR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1946
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M157 KCCGNSWTTT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M13127
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M116 KMCATNNWGGA in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M9024
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M120 KRCTCNNNNMANAGC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M12550
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M110 MCAATNNNNNGCG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M10166
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M138 MYAATNNNNNNNGGC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1716
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M125 RAAGNYNNCTTY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M9140
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M66 RACTNNRTTTNC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M17692
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M154 RNCTGNYNRNCTGNY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M10112
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M140 RNGTGGGC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M7513
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M122 RNTCANNRNNYNATTW in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M10206
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M129 RRAGTTGT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M9412
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M107 RTTTNNNYTGGM in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M6869
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M151 RYAAAKNNNNNNTTGW in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M5027
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M128 RYCACNNRNNRNCAG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M13510
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M133 RYTAAWNNNTGAY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M17216
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M87 RYTGCNWTGGNR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M399
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M62 SMTTTTGT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M2268
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M80 SNACANNNYSYAGA in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M3888
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M71 SYATTGTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1656
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M162 TAANNYSGCG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M6093
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M136 TAAYNRNNTCC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M7173
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M132 TCCATTKW in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1728
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M39 TCCCRNNRTGC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M13849
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M42 TGACATY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M10498
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M22 TGCGCANK in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M13012
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M92 TGCTGAY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1460
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M27 TGGNNNNNNKCCAR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M16032
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M117 TGTYNNNNNRGCARM in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M9573
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M8 TMTCGCGANR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M5721
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M75 TNCATNTCCYR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M3980
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M64 TTANTCA in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M9684
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M161 TTANWNANTGGM in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M402
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M72 TTCYRGAA in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M15966
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M169 TTTNNANAGCYR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M8368
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M152 WCAANNNYCAG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M12984
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M59 WCTCNATGGY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M17712
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M155 WGTTNNNNNAAA in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1328
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M174 WTGAAAT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M4815
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M46 WTTGKCTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M10416
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M127 WWTAAGGC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M7349
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M126 WYAAANNRNNNGCG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M8935
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M147 YAATNANRNNNCAG in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M10288
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M90 YAATNRNNNYNATT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M435
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M97 YATTNATC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M6052
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M58 YCATTAA in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M12349
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M149 YGACNNYACAR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M19578
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M96 YGCANTGCR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M17342
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M30 YGCGYRCGC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M849
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M109 YGTCCTTGR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1830
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M145 YKACATTT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M16291
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M170 YNGTTNNNATT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M18600
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M166 YNTTTNNNANGCARM in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M19571
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M156 YRCCAKNNGNCGC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M14861
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M115 YRTCANNRCGC in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1856
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M168 YTAAYNGCT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M2330
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M114 YTCCCRNNAGGY in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M5789
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M150 YTTCCNNNGGAMR in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1030
exact_source: R-HSA-174178
external_details_URL: https://www.reactome.org/content/detail/R-HSA-174178
source_species_code: HS
contributor: Reactome
contrib_organization: Reactome
description_brief:
  APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1


systematic_name: M27121
exact_source: R-HSA-210744
external_details_URL: https://www.reactome.org/content/detail/R-HSA-210744
source_species_code: HS
contributor: Reactome
contrib_organization: Reactome
description_brief:
  Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells


systematic_name: M27285
exact_source: R-HSA-381426
external_details_URL: https://www.reactome.org/content/detail/R-HSA-381426
source_species_code: HS
contributor: Reactome
contrib_organization: Reactome
description_brief:
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)


systematic_name: M897
exact_source: R-HSA-446193
external_details_URL: https://www.reactome.org/content/detail/R-HSA-446193
source_species_code: HS
contributor: Reactome
contrib_organization: Reactome
description_brief:
  Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein


systematic_name: M27629
exact_source: R-HSA-6803205
external_details_URL: https://www.reactome.org/content/detail/R-HSA-6803205
source_species_code: HS
contributor: Reactome
contrib_organization: Reactome
description_brief:
  TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain


systematic_name: M27634
exact_source: R-HSA-6804115
external_details_URL: https://www.reactome.org/content/detail/R-HSA-6804115
source_species_code: HS
contributor: Reactome
contrib_organization: Reactome
description_brief:
  TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain


systematic_name: M721
exact_source: R-HSA-72662
external_details_URL: https://www.reactome.org/content/detail/R-HSA-72662
source_species_code: HS
contributor: Reactome
contrib_organization: Reactome
description_brief:
  Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S


description_brief: Genes upregulated in Monocytes from Idiopathic Pulmonary Fibrosis Patients vs. Controls
systematic_name: M48277
exact_source: table_e4_degs_ipfvscontrol2, avg_LogFC>0, p_val_adg<0.05
source_species_code: HS
contributor: Anthony Castanza
contrib_organization: MSigDB Team
description_full:
  Thirty-eight PBMC samples from 25 patients with IPF and 13 matched controls yielded 149,564 cells that segregated into 23 subpopulations. Classical monocytes were increased in progressive and stable IPF compared to controls (32.1%, 25.2%, 17.9%, respectively, p<0.05). Total lymphocytes were decreased in IPF vs controls, and in progressive vs stable IPF (52.6% vs 62.6%, p=0.035). Tregs were increased in progressive vs stable IPF (1.8% vs 1.1% of all PBMC, p=0.007), although not different than controls, and may be associated with decreased survival (P=0.009 in Kaplan-Meier analysis; P=0.069 after adjusting for age, sex, and baseline FVC). Flow cytometry analysis confirmed this finding in an independent cohort of IPF patients. Fraction of Tregs out of all T cells was also increased in two cohorts of lung scRNA-seq. CCL22 and CCL18, ligands for CCR4 and CCR8 Treg chemotaxis receptors, were increased in IPF. The single-cell atlas of the peripheral immune system in IPF, reveals an outcome-predictive increase in classical monocytes and Tregs, as well as evidence for a lung-blood immune recruitment axis involving CCL7 (for classical monocytes) and CCL18/CCL22 (for Tregs). (From Abstract)


systematic_name: M48289
exact_source: table_e4_degs_ipfvscontrol2, avg_LogFC>0, p_val_adg<0.05
source_species_code: HS
contributor: Anthony Castanza
contrib_organization: MSigDB Team
description_brief:
  Genes upregulated in Treg cells from Progressive Idiopathic Pulmonary Fibrosis Patients vs. Stable Non-Progressors

description_full:
[cell repeats an earlier one in this file: 1198 characters]


systematic_name: M48290
exact_source: table_e4_degs_ipfvscontrol2, avg_LogFC<0, p_val_adg<0.05
source_species_code: HS
contributor: Anthony Castanza
contrib_organization: MSigDB Team
description_brief:
  Genes downregulated in Treg cells from Progressive Idiopathic Pulmonary Fibrosis Patients vs. Stable Non-Progressors

description_full:
[cell repeats an earlier one in this file: 1198 characters]


systematic_name: M48292
exact_source: table_e5_degs_progressivevsstable2, avg_LogFC<0, p_val_adg<0.05
source_species_code: HS
contributor: Anthony Castanza
contrib_organization: MSigDB Team
description_brief:
  Genes downregulated in Monocytes from Progressive Idiopathic Pulmonary Fibrosis Patients vs. Stable Non-Progressors

description_full:
[cell repeats an earlier one in this file: 1198 characters]


systematic_name: M48295
exact_source: table_e5_degs_progressivevsstable2, avg_LogFC>0, p_val_adg<0.05
source_species_code: HS
contributor: Anthony Castanza
contrib_organization: MSigDB Team
description_brief:
  Genes upregulated in C84 T-cells from Progressive Idiopathic Pulmonary Fibrosis Patients vs. Stable Non-Progressors

description_full:
[cell repeats an earlier one in this file: 1198 characters]


systematic_name: M48296
exact_source: table_e5_degs_progressivevsstable2, avg_LogFC<0, p_val_adg<0.05
source_species_code: HS
contributor: Anthony Castanza
contrib_organization: MSigDB Team
description_brief:
  Genes downregulated in CD8 T-cells from Progressive Idiopathic Pulmonary Fibrosis Patients vs. Stable Non-Progressors

description_full:
[cell repeats an earlier one in this file: 1198 characters]


systematic_name: M48298
exact_source: table_e5_degs_progressivevsstable2, avg_LogFC<0, p_val_adg<0.05
source_species_code: HS
contributor: Anthony Castanza
contrib_organization: MSigDB Team
description_brief:
  Genes downregulated in B cells from Progressive Idiopathic Pulmonary Fibrosis Patients vs. Stable Non-Progressors

description_full:
[cell repeats an earlier one in this file: 1198 characters]


systematic_name: M48299
exact_source: table_e5_degs_progressivevsstable2, avg_LogFC>0, p_val_adg<0.05
source_species_code: HS
contributor: Anthony Castanza
contrib_organization: MSigDB Team
description_brief:
  Genes upregulated in NK cells from Progressive Idiopathic Pulmonary Fibrosis Patients vs. Stable Non-Progressors

description_full:
[cell repeats an earlier one in this file: 1198 characters]


systematic_name: M48300
exact_source: table_e5_degs_progressivevsstable2, avg_LogFC<0, p_val_adg<0.05
source_species_code: HS
contributor: Anthony Castanza
contrib_organization: MSigDB Team
description_brief:
  Genes downregulated in NK cells from Progressive Idiopathic Pulmonary Fibrosis Patients vs. Stable Non-Progressors

description_full:
[cell repeats an earlier one in this file: 1198 characters]


systematic_name: M1265
exact_source: Table 1
source_species_code: RN
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Selected genes up-regulated in Rat1Ras cells (fibroblasts) which were transformed by expression of an oncogenic activated form of HRAS [GeneID=3265] compared to the parental Rat1 cells.

description_full:
  Heat shock proteins (Hsps) are overexpressed in many tumors, but are downregulated in some tumors. To check for a direct effect of Ha-Ras(val12) on HSP70 transcription, we transiently expressed the oncoprotein in Rat1 fibroblasts and monitored its effect on HSP70b promoter-driven reporter gene. We show that expression of Ha-Ras(val12) induced this promoter. Promoter analysis via systematic deletions and point mutations revealed that Ha-Ras(val12) induces HSP70b transcription via heat shock elements (HSEs). Also, Ha-Ras(val12) induction of HSE-mediated transcription was dramatically reduced in HSF1-/- cells. Yet, residual effect of Ha-Ras(val12) that was still measured in HSF1-/- cells suggests that some of the Ha-Ras(val12) effect is Hsf1-independent. When HSF1-/- cells, stably expressing Ha-Ras(val12), were grown on soft agar only small colonies were formed suggesting a role for heat shock factor 1 (Hsf1) in Ha-Ras(val12)-mediated transformation. Although Ha-ras(Val12) seems to be an inducer of HSP70's expression, we found that in Ha-ras(Val12-)transformed fibroblasts expression of this gene is suppressed. This suppression is correlated with higher sensitivity of Ha-ras(val12)-transformed cells to heat shock. We suggest that Ha-ras(Val12) is involved in Hsf1 activation, thereby inducing the cellular protective response. Cells that repress this response are perhaps those that acquire the capability to further proliferate and become transformed clones.


systematic_name: M16909
exact_source: Table 1S
source_species_code: HS
GEO_id: E-MEXP-958
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in HepaRG cells (liver cancer) expressing constituvely active form of MTOR [GeneID=2475].

description_full:
  The mammalian target of rapamycin (mTOR) pathway, a major regulator of translation, is frequently activated in hepatocellular carcinomas. We investigated the effects of mTOR activation in the human HepaRG cells, which possess potent hepatocytic differentiation capability. Differentiation of HepaRG cells into functional and polarized hepatocyte-like cells correlated with a decrease in mTOR and Akt activities. Stable cell lines expressing an activated mutant of mTOR were generated. Sustained activation of mTOR impaired the hepatocytic differentiation capability of these cells as shown by impaired formation of bile canaliculi, absence of polarity, and reduced secretion of alpha1-antitrypsin. An inhibitor of mTOR, rapamycin, was able to revert this phenotype. Furthermore, increased mTOR activity in HepaRG cells resulted in their resistance to the antiproliferative effects of transforming growth factor-beta1. Profiling of polysome-bound transcripts indicated that activated mTOR specifically targeted genes posttranscriptionally regulated on hepatocytic differentiation. Three major biological networks targeted by activated mTOR were identified: (a) cell death associated with tumor necrosis factor superfamily members, IFNs and caspases; (b) lipid homeostasis associated with the transcription factors PPARalpha, PPARdelta, and retinoid X receptor beta; and (c) liver development associated with CCAAT/enhancer binding protein alpha and hepatic mitogens. In conclusion, increased mTOR activity conferred a preneoplastic phenotype to the HepaRG cells by altering the translation of genes vital for establishing normal hepatic energy homeostasis and moderating hepatocellular growth.


systematic_name: M14371
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE7824
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Down-regulated genes in peripheral zone of human pancreatic cancer growing in the pancreas of nude mice compared to that of the tumor from the central zone.

description_full:
  Using Affymetrix HG-U133 Plus 2.0 array and laser capture microdissection techniques, we determined whether different zones of the same pancreatic tumor exhibited differential expression of genes. Human L3.6pl pancreatic cancer cells were implanted into the pancreas of nude mice. Three weeks later when tumors were 7 to 9 mm in diameter, gene expression patterns in tumor cells within the central and peripheral zones were compared, and 1,222 genes showed statistically significant differences. Bioinformatic functional analysis revealed that 346 up-regulated genes in the peripheral zone were related to cytoskeleton organization and biogenesis, cell cycle, cell adhesion, cell motility, DNA replication, localization, integrin-mediated signaling pathway, development, morphogenesis, and IkappaB kinase/nuclear factor-kappaB cascade; 876 up-regulated genes in the central zone were related to regulation of cell proliferation, regulation of transcription, transmembrane receptor protein tyrosine kinase signaling pathways, response to stress, small GTPase-mediated signal transduction, hexose metabolism, cell death, response to external stimulus, carbohydrate metabolism, and response to wounding. The reliability of the microarray results were confirmed by in situ hybridization analysis of the expression of two genes. Collectively, the data showed zonal heterogeneity for gene expression profiles in tumors and suggest that characterization of zonal gene expression profiles is essential if microarray analyses of genetic profiles are to produce reproducible data, predict disease prognosis, and allow design of specific therapeutics.


description_brief: Up-regulated genes in angioimmunoblastic lymphoma (AILT) compared to normal T lymphocytes.
systematic_name: M12225
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE6338
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Angioimmunoblastic lymphoma (AILT) is the second most common subtype of peripheral T-cell lymphoma (PTCL) and is characterized by dismal prognosis. Thus far, only a few studies have dealt with its molecular pathogenesis. We performed gene expression profile (GEP) analysis of six AILT, six anaplastic large cell lymphomas (ALCL), 28 PTCL-unspecified (PTCL/U), and 20 samples of normal T lymphocytes (including CD4(+), CD8(+), and activated and resting subpopulations), aiming to (a) assess the relationship of AILT with other PTCLs, (b) establish the relationship between AILT and normal T-cell subsets, and (c) recognize the cellular programs deregulated in AILT possibly looking for novel potential therapeutic targets. First, we found that AILT and other PTCLs have rather similar GEP, possibly sharing common oncogenic pathways. Second, we found that AILTs are closer to activated CD4(+), rather than to resting or CD8(+) lymphocytes. Furthermore, we found that the molecular signature of follicular T helper cells was significantly overexpressed in AILT, reinforcing the idea that AILT may arise from such cellular counterpart. Finally, we identified several genes deregulated in AILT, including PDGFRA, REL, and VEGF. The expression of several molecules was then studied by immunohistochemistry on tissue microarrays containing 45 independent AILT cases. Notably, we found that the vascular endothelial growth factor (VEGF) was expressed not only by reactive cells, but also by neoplastic cells, and that nuclear factor-kappaB (NF-kappaB) activation is uncommon in AILT, as suggested by frequent exclusively cytoplasmic c-REL localization. Our study provides new relevant information on AILT biology and new candidates for possible therapeutic targets such as PDGFRA (platelet-derived growth factor alpha) and VEGF.


systematic_name: M6663
exact_source: Table 1S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in DLBCL (diffuse large B-cell lymphoma) cell lines sensitive to stimulation of CD40 [GeneID=958] relative to the resistant ones.

description_full:
  CD40 promotes survival, proliferation, and differentiation of normal B cells but can cause activation-induced cell death in malignant B lymphocytes. CD40 ligand and anti-CD40 antibodies have been used successfully to induce apoptosis in lymphoma lines both in vitro and in xenograft tumor models. Although this makes CD40 an attractive target for antitumor therapies, the response of malignant B cells to CD40 signaling is variable, and CD40 stimulation can enhance proliferation and can increase chemoresistance in some cell lines. It would therefore be useful to identify markers that predict whether a specific cell line or tumor will undergo apoptosis when stimulated with CD40 and to identify targets downstream of CD40 that affect only the apoptotic arm of CD40 signaling. We have analyzed gene expression patterns in CD40-sensitive and CD40-resistant diffuse large B-cell lymphoma (DLBCL) cell lines to identify signaling pathways that are involved in CD40-mediated apoptosis. CD40-resistant lines expressed pre-B-cell markers, including RAG and VPREB, whereas CD40-sensitive cells resembled mature B cells and expressed higher levels of transcripts encoding several members of the CD40 signaling pathway, including LCK and VAV. In addition, CD40-sensitive DLBCL cell lines also displayed constitutive activation of extracellular signal-regulated kinase (ERK) and failed to undergo apoptosis when ERK phosphorylation was inhibited. In contrast, CD40-resistant lines showed no constitutive activation of ERK and no increase in ERK activity in response to CD40 stimulation. Our results suggest that constitutive activation of ERK may be required for death signaling by CD40.


systematic_name: M17287
exact_source: Table 2S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in LNCaP cells (prostate cancer) by overexpression of SOX4 [GeneID=6659] and up-regulated by its RNAi knockdown.

description_full:
[cell repeats an earlier one in this file: 1100 characters]


description_brief: Genes up-regulated in uveal melanoma: class 2 vs class 1 tumors.
systematic_name: M12490
exact_source: Table 2S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Microarray gene expression profiling is a powerful tool for generating molecular cancer classifications. However, elucidating biological insights from these large data sets has been challenging. Previously, we identified a gene expression-based classification of primary uveal melanomas that accurately predicts metastatic death. Class 1 tumors have a low risk and class 2 tumors a high risk for metastatic death. Here, we used genes that discriminate these tumor classes to identify biological correlates of the aggressive class 2 signature. A search for Gene Ontology categories enriched in our class-discriminating gene list revealed a global down-regulation of neural crest and melanocyte-specific genes and an up-regulation of epithelial genes in class 2 tumors. Correspondingly, class 2 tumors exhibited epithelial features, such as polygonal cell morphology, up-regulation of the epithelial adhesion molecule E-cadherin, colocalization of E-cadherin and beta-catenin to the plasma membrane, and formation of cell-cell adhesions and acinar structures. One of our top class-discriminating genes was the helix-loop-helix inhibitor ID2, which was strongly down-regulated in class 2 tumors. The class 2 phenotype could be recapitulated by eliminating Id2 in cultured class 1 human uveal melanoma cells and in a mouse ocular melanoma model. Id2 seemed to suppress the epithelial-like class 2 phenotype by inhibiting an activator of the E-cadherin promoter. Consequently, Id2 loss triggered up-regulation of E-cadherin, which in turn promoted anchorage-independent cell growth, a likely antecedent to metastasis. These findings reveal new roles for Id2 and E-cadherin in uveal melanoma progression, and they identify potential targets for therapeutic intervention.


systematic_name: M17471
exact_source: Table 3S
source_species_code: HS
GEO_id: GSE3893
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in invasive ductal carcinoma (IDC) relative to ductal carcinoma in situ (DCIS, non-invasive).

description_full:
  Becoming invasive is a crucial step in breast cancer oncogenesis. At this point, a lesion carries the potential for spreading and metastasis--a process, whose molecular characteristics still remain poorly understood. In this article, we describe a matched-pair analysis of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of nine breast ductal carcinomas to identify novel molecular markers characterizing the transition from DCIS to IDC. The purpose of this study was to better understand the molecular biology of this transition and to identify candidate genes whose products might serve as prognostic markers and/or as molecular targets for treatment. To obtain cellular-based gene expression profiles from epithelial tumor cells, we combined laser capture microdissection with a T7-based two-round RNA amplification and Affymetrix oligonucleotide microarray analysis. Altogether, a set of 24 tumor samples was analyzed, comprised of nine matched DCIS/IDC and replicate DCIS/IDC preparations from three of the nine tumors. Cluster analysis on expression data shows the robustness and reproducibility of the techniques we established. Using multiple statistical methods, 546 significantly differentially expressed probe sets were identified. Eighteen candidate genes were evaluated by RT-PCR. Examples of genes already known to be associated with breast cancer invasion are BPAG1, LRRC15, MMP11, and PLAU. The expression of BPAG1, DACT1, GREM1, MEF2C, SART2, and TNFAIP6 was localized to epithelial tumor cells by in situ hybridization and/or immunohistochemistry, confirming the accuracy of laser capture microdissection sampling and microarray analysis.


systematic_name: M126
exact_source: Table 3S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in glioma cell lines treated with both decitabine [PubChem=451668] and TSA [PubChem=5562].

description_full:
  Malignant glioma is the most common central nervous system tumor of adults and is associated with a significant degree of morbidity and mortality. Gliomas are highly invasive and respond poorly to conventional treatments. Gliomas, like other tumor types, arise from a complex and poorly understood sequence of genetic and epigenetic alterations. Epigenetic alterations leading to gene silencing, in the form of aberrant CpG island promoter hypermethylation and histone deacetylation, have not been thoroughly investigated in brain tumors, and elucidating such changes is likely to enhance our understanding of their etiology and provide new treatment options. We used a combined approach of pharmacologic inhibition of DNA methylation and histone deacetylation, coupled with expression microarrays, to identify novel targets of epigenetic silencing in glioma cell lines. From this analysis, we identified >160 genes up-regulated by 5-aza-2'-deoxycytidine and trichostatin A treatment. Further characterization of 10 of these genes, including the putative metastasis suppressor CST6, the apoptosis-inducer BIK, and TSPYL5, whose function is unknown, revealed that they are frequent targets of epigenetic silencing in glioma cell lines and primary tumors and suppress glioma cell growth in culture. Furthermore, we show that other members of the TSPYL gene family are epigenetically silenced in gliomas and dissect the contribution of individual DNA methyltransferases to the aberrant promoter hypermethylation events. These studies, therefore, lay the foundation for a comprehensive understanding of the full extent of epigenetic changes in gliomas and how they may be exploited for therapeutic purposes.


systematic_name: M19016
exact_source: Table 1S: E population: f.ch.<0
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in erythroid progenitor cells isolated from bone marrow of patients with Diamond-Blackfan anemia (DBA) and mutated RPS19 [GeneID=6223].

description_full:
[cell repeats an earlier one in this file: 1452 characters]


systematic_name: M3019
exact_source: Table S1: Fold change > 1 (red)
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in 3 out of 4 NSCLC cell lines (non-small cell lung cancer) after treatment with azacitidine [PubChem=9444] and TSA [PubChem=5562].

description_full:
  Lung cancer is the leading cause of cancer-related deaths in the United States due, in large part, to the lack of early detection methods. Lung cancer arises from a complex series of genetic and epigenetic changes leading to uncontrolled cell growth and metastasis. Unlike genetic changes, epigenetic changes, such as DNA methylation and histone acetylation, are reversible with currently available pharmaceuticals and are early events in lung tumorigenesis detectable by non-invasive methods. In order to better understand how epigenetic changes contribute to lung cancer, and to identify new disease biomarkers, we combined pharmacologic inhibition of DNA methylation and histone deacetylation in non-small cell lung cancer (NSCLC) cell lines, with genome-wide expression profiling. Of the more than 200 genes upregulated by these treatments, three of these, neuronatin, metallothionein 3 and cystatin E/M, were frequently hypermethylated and transcriptionally downregulated in NSCLC cell lines and tumors. Interestingly, four other genes, cylindromatosis, CD9, activating transcription factor 3 and oxytocin receptor, were dominantly regulated by histone deacetylation and were also frequently downregulated in lung tumors. The majority of these genes also suppressed NSCLC growth in culture when ectopically expressed. This study therefore reveals new putative NSCLC growth regulatory genes and epigenetic disease biomarkers that may enhance early detection strategies and serve as therapeutic targets.


systematic_name: M8519
exact_source: Table 2S: Mean Fold-Difference < 0
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in mARMS (molecular ARMS) compared to the mERMS (molecular ERMS) class of rhabdomyosarcoma tumors.

description_full:
[cell repeats an earlier one in this file: 1766 characters]


systematic_name: M19488
exact_source: Table 9S
source_species_code: HS
GEO_id: GSE12452
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in nasopharyngeal carcinoma (NPC) positive for LMP1 [GeneID=9260], a latent gene of Epstein-Barr virus (EBV).

description_full:
[cell repeats an earlier one in this file: 1543 characters]


systematic_name: M6659
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE4984
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in monocyte-derived dendritic cells (MDDC) after stimulation with galecin-1 (lectin, LGALS1) [GeneID=3956] compared to that with bacterial lipopolysaccharide (LPS).

description_full:
  Dendritic cells (DCs) are potent mediators of the immune response, and can be activated by exogenous pathogen components. Galectin-1 is a member of the conserved beta-galactoside-binding lectin family that binds galactoside residues on cell surface glycoconjugates. Galectin-1 is known to play a role in immune regulation via action on multiple immune cells. However, its effects on human DCs are unknown. In this study, we show that galectin-1 induces a phenotypic and functional maturation in human monocyte-derived DCs (MDDCs) similar to but distinct from the activity of the exogenous pathogen stimuli, LPS. Immature human MDDCs exposed to galectin-1 up-regulated cell surface markers characteristic of DC maturation (CD40, CD83, CD86, and HLA-DR), secreted high levels of IL-6 and TNF-alpha, stimulated T cell proliferation, and showed reduced endocytic capacity, similar to LPS-matured MDDCs. However, unlike LPS-matured DCs, galectin-1-treated MDDCs did not produce the Th1-polarizing cytokine IL-12. Microarray analysis revealed that in addition to modulating many of the same DC maturation genes as LPS, galectin-1 also uniquely up-regulated a significant subset of genes related to cell migration through the extracellular matrix (ECM). Indeed, compared with LPS, galectin-1-treated human MDDCs exhibited significantly better chemotactic migration through Matrigel, an in vitro ECM model. Our findings show that galectin-1 is a novel endogenous activator of human MDDCs that up-regulates a significant subset of genes distinct from those regulated by a model exogenous stimulus (LPS). One unique effect of galectin-1 is to increase DC migration through the ECM, suggesting that galectin-1 may be an important component in initiating an immune response.


systematic_name: M4785
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE4984
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in monocyte-derived dendritic cells (MDDC) after stimulation with galecin-1 (lectin, LGALS1) [GeneID=3956] compared to that with bacterial lipopolysaccharide (LPS).

description_full:
  Dendritic cells (DCs) are potent mediators of the immune response, and can be activated by exogenous pathogen components. Galectin-1 is a member of the conserved beta-galactoside-binding lectin family that binds galactoside residues on cell surface glycoconjugates. Galectin-1 is known to play a role in immune regulation via action on multiple immune cells. However, its effects on human DCs are unknown. In this study, we show that galectin-1 induces a phenotypic and functional maturation in human monocyte-derived DCs (MDDCs) similar to but distinct from the activity of the exogenous pathogen stimuli, LPS. Immature human MDDCs exposed to galectin-1 up-regulated cell surface markers characteristic of DC maturation (CD40, CD83, CD86, and HLA-DR), secreted high levels of IL-6 and TNF-alpha, stimulated T cell proliferation, and showed reduced endocytic capacity, similar to LPS-matured MDDCs. However, unlike LPS-matured DCs, galectin-1-treated MDDCs did not produce the Th1-polarizing cytokine IL-12. Microarray analysis revealed that in addition to modulating many of the same DC maturation genes as LPS, galectin-1 also uniquely up-regulated a significant subset of genes related to cell migration through the extracellular matrix (ECM). Indeed, compared with LPS, galectin-1-treated human MDDCs exhibited significantly better chemotactic migration through Matrigel, an in vitro ECM model. Our findings show that galectin-1 is a novel endogenous activator of human MDDCs that up-regulates a significant subset of genes distinct from those regulated by a model exogenous stimulus (LPS). One unique effect of galectin-1 is to increase DC migration through the ECM, suggesting that galectin-1 may be an important component in initiating an immune response.


systematic_name: M17693
exact_source: Table 1S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in Daudi cells (B lymphocytes) stably expressing CD5 [GeneID=921] off a plasmid vector.

description_full:
  Chronic lymphocytic leukemia (CLL) results in the accumulation of B cells, presumably reflecting the selection of malignant cell precursors with Ag combined with complex alterations in protein activity. Repeated BCR stimulation of normal B cells leads to anergy and CD5 expression, both of which are features of CLL. Because CD5 is phosphorylated on tyrosine following BCR engagement and negatively regulates BCR signaling in normal B cells, we investigated its phosphorylation status and found it to be naturally phosphorylated on tyrosine but not on serine residues in CLL samples. To analyze the role of CD5, we established a B cell line in which CD5 is phosphorylated. Gene profiling of vector vs CD5-transfected B cells pointed out gene groups whose expression was enhanced: Apoptosis inhibitors (BCL2), NF-kappaB (RELB, BCL3), Wnt, TGFbeta, VEGF, MAPKs, Stats, cytokines, chemokines (IL-10, IL-10R, IL-2R, CCL-3, CCL-4, and CCR7), TLR-9, and the surface Ags CD52, CD54, CD70, and CD72. Most of these gene groups are strongly expressed in CLL B cells as compared with normal B cells. Unexpectedly, metabolic pathways, namely cholesterol synthesis and adipogenesis, are also enhanced by CD5. Conversely, CD5 inhibited genes involved in RNA splicing and processing, ribosome biogenesis, proteasome, and CD80 and CD86 Ags, whose expression is low in CLL. Comparison of CD5- vs tailless CD5-transfected cells further demonstrated the role of CD5 phosphorylation in the regulation of selected genes. These results support a model where CLL cells are chronically stimulated, leading to CD5 activation and cell survival. In addition to CD5 itself, we point to several CD5-induced genes as potential therapeutic targets.


systematic_name: M13893
exact_source: Table 2S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in Daudi cells (B lymphocytes) stably expressing CD5 [GeneID=921] off a plasmid vector.

description_full:
  Chronic lymphocytic leukemia (CLL) results in the accumulation of B cells, presumably reflecting the selection of malignant cell precursors with Ag combined with complex alterations in protein activity. Repeated BCR stimulation of normal B cells leads to anergy and CD5 expression, both of which are features of CLL. Because CD5 is phosphorylated on tyrosine following BCR engagement and negatively regulates BCR signaling in normal B cells, we investigated its phosphorylation status and found it to be naturally phosphorylated on tyrosine but not on serine residues in CLL samples. To analyze the role of CD5, we established a B cell line in which CD5 is phosphorylated. Gene profiling of vector vs CD5-transfected B cells pointed out gene groups whose expression was enhanced: Apoptosis inhibitors (BCL2), NF-kappaB (RELB, BCL3), Wnt, TGFbeta, VEGF, MAPKs, Stats, cytokines, chemokines (IL-10, IL-10R, IL-2R, CCL-3, CCL-4, and CCR7), TLR-9, and the surface Ags CD52, CD54, CD70, and CD72. Most of these gene groups are strongly expressed in CLL B cells as compared with normal B cells. Unexpectedly, metabolic pathways, namely cholesterol synthesis and adipogenesis, are also enhanced by CD5. Conversely, CD5 inhibited genes involved in RNA splicing and processing, ribosome biogenesis, proteasome, and CD80 and CD86 Ags, whose expression is low in CLL. Comparison of CD5- vs tailless CD5-transfected cells further demonstrated the role of CD5 phosphorylation in the regulation of selected genes. These results support a model where CLL cells are chronically stimulated, leading to CD5 activation and cell survival. In addition to CD5 itself, we point to several CD5-induced genes as potential therapeutic targets.


systematic_name: M14801
exact_source: Table S1 Fold change < 0.5
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in PC-3 cells (prostate cancer) stably expressing ST7 [GeneID=7982] off a plasmid vector.

description_full:
  Multiple lines of evidence have provided compelling evidence for the existence of a tumor suppressor gene (TSG) on chromosome 7q31.1. ST7 may be the target of this genetic instability but its designation as a TSG is controversial. In this study, we show that, functionally, ST7 behaves as a tumor suppressor in human cancer. ST7 suppressed growth of PC-3 prostate cancer cells inoculated subcutaneously into severe combined immunodeficient mice, and increased the latency of tumor detection from 13 days in control tumors to 23 days. Re-expression of ST7 was also associated with suppression of colony formation under anchorage-independent conditions in MDA-MB-231 breast cancer cells and ST7 mRNA expression was downregulated in 44% of primary breast cancers. Expression profiling of PC-3 cells revealed that ST7 predominantly induces changes in genes involved in re-modeling the extracellular matrix such as SPARC, IGFBP5 and several matrix metalloproteinases. These data indicate that ST7 may mediate tumor suppression through modification of the tumor microenvironment.


systematic_name: M18635
exact_source: Table 2S
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in APL (acute promyeolocytic leukemia) blasts expressing PML-RARA fusion [GeneID=5371;5914] compared to normal promyeloblasts.

description_full:
  Acute promyelocytic leukemia (APL) is a clonal expansion of hematopoietic precursors blocked at the promyelocytic stage. Gene expression profiles of APL cells obtained from 16 patients were compared to eight samples of CD34+-derived normal promyelocytes. Malignant promyelocytes showed widespread changes in transcription in comparison to their normal counterpart and 1020 differentially expressed genes were identified. Discriminating genes include transcriptional regulators (FOS, JUN and HOX genes) and genes involved in cell cycle and DNA repair. The strong upregulation in APL of some transcripts (FLT3, CD33, CD44 and HGF) was also confirmed at protein level. Interestingly, a trend toward a transcriptional repression of genes involved in different DNA repair pathways was found in APL and confirmed by real-time polymerase chain reactor (PCR) in a new set of nine APLs. Our results suggest that both inefficient base excision repair and recombinational repair might play a role in APLs development. To investigate the expression pathways underlying the development of APL occurring as a second malignancy (sAPL), we included in our study eight cases of sAPL. Although both secondary and de novo APL were characterized by a strong homogeneity in expression profiling, we identified a small set of differentially expressed genes that discriminate sAPL from de novo cases.


systematic_name: M19993
exact_source: Table 3S: Fold change >= 2
source_species_code: HS
GEO_id: GSE4392
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Up-regulated genes in B-CLL (B-cell chronic leukemia) patients expressing high levels of ZAP70 and CD38 [GeneID=7535;952], which are associated with poor survival.

description_full:
  B-cell chronic lymphocytic leukaemia (B-CLL) is a heterogenous disease with a highly variable clinical course and analysis of zeta-associated protein 70 (ZAP-70) and CD38 expression on B-CLL cells allowed for identification of patients with good (ZAP-70-CD38-) and poor (ZAP-70+CD38+) prognosis. DNA microarray technology was employed to compare eight ZAP-70+CD38+ with eight ZAP-70-CD38- B-CLL cases. The expression of 358 genes differed significantly between the two subgroups, including genes involved in B-cell receptor signaling, angiogenesis and lymphomagenesis. Three of these genes, that is, immune receptor translocation-associated protein 4 (IRTA4)/Fc receptor homologue 2 (FcRH2), angiopoietin 2 (ANGPT2) and Pim2 were selected for further validating studies in a cohort of 94 B-CLL patients. IRTA4/FcRH2 expression as detected by flow cytometry was significantly lower in the poor prognosis subgroup as compared to ZAP-70-CD38- B-CLL cells. In healthy individuals, IRTA4/FcRH2 protein expression was associated with a CD19+CD27+ memory cell phenotype. ANGPT2 plasma concentrations were twofold higher in the poor prognosis subgroup (P<0.05). Pim2 was significantly overexpressed in poor prognosis cases and Binet stage C. Disease progression may be related to proangiogenic processes and strong Pim2 expression.


systematic_name: M535
exact_source: Table 2S: Fold Change > 1
source_species_code: HS
GEO_id: GSE5550
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in CD34+ [GeneID=947] cells isolated from bone marrow of CML (chronic myelogenous leukemia) patients, compared to those from normal donors.

description_full:
  In this study, we provide a molecular signature of highly enriched CD34+ cells from bone marrow of untreated patients with chronic myelogenous leukemia (CML) in chronic phase in comparison with normal CD34+ cells using microarrays covering 8746 genes. Expression data reflected several BCR-ABL-induced effects in primary CML progenitors, such as transcriptional activation of the classical mitogen-activated protein kinase pathway and the phosphoinositide-3 kinase/AKT pathway as well as downregulation of the proapoptotic gene IRF8. Moreover, novel transcriptional changes in comparison with normal CD34+ cells were identified. These include upregulation of genes involved in the transforming growth factorbeta pathway, fetal hemoglobin genes, leptin receptor, sorcin, tissue inhibitor of metalloproteinase 1, the neuroepithelial cell transforming gene 1 and downregulation of selenoprotein P. Additionally, genes associated with early hematopoietic stem cells (HSC) and leukemogenesis such as HoxA9 and MEIS1 were transcriptionally activated. Differential expression of differentiation-associated genes suggested an altered composition of the CD34+ cell population in CML. This was confirmed by subset analyses of chronic phase CML CD34+ cells showing an increase of the proportion of megakaryocyte-erythroid progenitors, whereas the proportion of HSC and granulocyte-macrophage progenitors was decreased in CML. In conclusion, our results give novel insights into the biology of CML and could provide the basis for identification of new therapeutic targets.


systematic_name: M17778
exact_source: Table 2S: Fold Change < 1
source_species_code: HS
GEO_id: GSE5550
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in CD34+ [GeneID=947] cells isolated from bone marrow of CML (chronic myelogenous leukemia) patients, compared to those from normal donors.

description_full:
  In this study, we provide a molecular signature of highly enriched CD34+ cells from bone marrow of untreated patients with chronic myelogenous leukemia (CML) in chronic phase in comparison with normal CD34+ cells using microarrays covering 8746 genes. Expression data reflected several BCR-ABL-induced effects in primary CML progenitors, such as transcriptional activation of the classical mitogen-activated protein kinase pathway and the phosphoinositide-3 kinase/AKT pathway as well as downregulation of the proapoptotic gene IRF8. Moreover, novel transcriptional changes in comparison with normal CD34+ cells were identified. These include upregulation of genes involved in the transforming growth factorbeta pathway, fetal hemoglobin genes, leptin receptor, sorcin, tissue inhibitor of metalloproteinase 1, the neuroepithelial cell transforming gene 1 and downregulation of selenoprotein P. Additionally, genes associated with early hematopoietic stem cells (HSC) and leukemogenesis such as HoxA9 and MEIS1 were transcriptionally activated. Differential expression of differentiation-associated genes suggested an altered composition of the CD34+ cell population in CML. This was confirmed by subset analyses of chronic phase CML CD34+ cells showing an increase of the proportion of megakaryocyte-erythroid progenitors, whereas the proportion of HSC and granulocyte-macrophage progenitors was decreased in CML. In conclusion, our results give novel insights into the biology of CML and could provide the basis for identification of new therapeutic targets.


systematic_name: M12570
exact_source: Table 2S: Ratio (T-PLL/ND) =< 0.5
source_species_code: HS
GEO_id: GSE5788
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in T-PLL cells (T-cell prolymphocytic leukemia) bearing the inv(14)/t(14:14) chromosomal aberration.

description_full:
  T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive lymphoma derived from mature T cells, which is, in most cases, characterized by the presence of an inv(14)(q11q32)/t(14;14)(q11;q32) and a characteristic pattern of secondary chromosomal aberrations. DNA microarray technology was employed to compare the transcriptomes of eight immunomagnetically purified CD3+ normal donor-derived peripheral blood cell samples, with five highly purified inv(14)/t(14;14)-positive T-PLL blood samples. Between the two experimental groups, 734 genes were identified as differentially expressed, including functionally important genes involved in lymphomagenesis, cell cycle regulation, apoptosis and DNA repair. Notably, the differentially expressed genes were found to be significantly enriched in genomic regions affected by recurrent chromosomal imbalances. Upregulated genes clustered on chromosome arms 6p and 8q, and downregulated genes on 6q, 8p, 10p, 11q and 18p. High-resolution copy-number determination using single nucleotide polymorphism chip technology in 12 inv(14)/t(14;14)-positive T-PLL including those analyzed for gene expression, refined chromosomal breakpoints as well as regions of imbalances. In conclusion, combined transcriptional and molecular cytogenetic profiling identified novel specific chromosomal loci and genes that are likely to be involved in disease progression and suggests a gene dosage effect as a pathogenic mechanism in T-PLL.


systematic_name: M9192
exact_source: Table 3S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in luminal-like breast cancer cell lines compared to the mesenchymal-like ones.

description_full:
  A better molecular characterization of breast cell lines (BCL) may help discover new markers to apply to tumour samples. We performed gene and protein expression profiling of 31 BCL using whole-genome DNA microarrays and immunohistochemistry (IHC) on 'cell microarrays' (CMA), respectively. Global hierarchical clustering discriminated two groups of BCL: group I corresponded to luminal cell lines, group II to basal and mesenchymal cell lines. Correlations with centroids calculated from a published 'intrinsic 500-gene set' assigned 15 cell lines as luminal, eight as basal and four as mesenchymal. A set of 1.233 genes was differentially expressed between basal and luminal samples. Mesenchymal and basal subtypes were rather similar and discriminated by only 227 genes. The expression of 10 proteins (CAV1, CD44, EGFR, MET, ETS1, GATA3, luminal cytokeratin CK19, basal cytokeratin CK5/6, CD10, and ERM protein moesin) encoded by luminal vs basal discriminator genes confirmed the subtype classification and the validity of the identified markers. Our BCL basal/luminal signature correctly re-classified the published series of tumour samples that originally served to identify the molecular subtypes, suggesting that the identified markers should be useful for tumour classification and might represent promising targets for disease management.


systematic_name: M12816
exact_source: Table 3S: Fold Change < 1
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in MDA-MB-453 cells (class A ER(-) [GeneID=2099] breast cancer) after exposure to the androgen R1881 [PubChem=13766].

description_full:
  Little is known of the underlying biology of estrogen receptor-negative, progesterone receptor-negative (ER(-)/PR(-)) breast cancer (BC), and few targeted therapies are available. Clinical heterogeneity of ER(-)/PR(-) tumors suggests that molecular subsets exist. We performed genome-wide expression analysis of 99 primary BC samples and eight BC cell lines in an effort to reveal distinct subsets, provide insight into their biology and potentially identify new therapeutic targets. We identified a subset of ER(-)/PR(-) tumors with paradoxical expression of genes known to be either direct targets of ER, responsive to estrogen, or typically expressed in ER(+) BC. Differentially expressed genes included SPDEF, FOXA1, XBP1, CYB5, TFF3, NAT1, APOD, ALCAM and AR (P<0.001). A classification model based on the expression signature of this tumor class identified molecularly similar BCs in an independent human BC data set and among BC cell lines (MDA-MB-453). This cell line demonstrated a proliferative response to androgen in an androgen receptor-dependent and ER-independent manner. In addition, the androgen-induced transcriptional program of MDA-MB-453 significantly overlapped the molecular signature of the unique ER(-)/PR(-) subclass of human tumors. This subset of BCs, characterized by a hormonally regulated transcriptional program and response to androgen, suggests the potential for therapeutic strategies targeting the androgen signaling pathway.


systematic_name: M1973
exact_source: Table 4S
source_species_code: HS
GEO_id: GSE2327
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in primary endothelial cells (HUVEC) after knockdown of WTAP [GeneID=9589] by RNAi.

description_full:
  Wilms' tumor 1-associating protein (WTAP) has been reported to be a ubiquitously expressed nuclear protein. Although a relation to splicing factors has been postulated, its actual physiological function still remains to be elucidated. To investigate the role of WTAP, we generated WTAP-knockout mice and performed small interfering RNA (siRNA)-mediated knockdown analyses in primary cultured cells. In DNA microarrays using human umbilical vein endothelial cells, WTAP-targeted siRNA treatment resulted in markedly reduced expression of cell-cycle-related genes. siRNA-mediated WTAP knockdown down-regulated the stability of cyclin A2 mRNA through a nine-nucleotide essential sequence in cyclin A2 mRNA 3' UTR. WTAP knockdown induced G2 accumulation, which is partially rescued by adenoviral overexpression of cyclin A2. Moreover, WTAP-null mice exhibited proliferative failure with death resulting at approximately embryonic day 6.5, an etiology almost identical to cyclin A2-null mice. Collectively, these findings establish WTAP as an essential factor for the stabilization of cyclin A2 mRNA, thereby regulating G2/M cell-cycle transition.


systematic_name: M4502
exact_source: Table 4S: Under-expressed lists
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in leukemic stem cells (LSC), defined as CD34+CD38- [GeneID=947;952] cells from AML (acute myeloid leukemia patients) compared to the CD34+CD38+ cells.

description_full:
  Tumors contain a fraction of cancer stem cells that maintain the propagation of the disease. The CD34(+)CD38(-) cells, isolated from acute myeloid leukemia (AML), were shown to be enriched leukemic stem cells (LSC). We isolated the CD34(+)CD38(-) cell fraction from AML and compared their gene expression profiles to the CD34(+)CD38(+) cell fraction, using microarrays. We found 409 genes that were at least twofold over- or underexpressed between the two cell populations. These include underexpression of DNA repair, signal transduction and cell cycle genes, consistent with the relative quiescence of stem cells, and chromosomal aberrations and mutations of leukemic cells. Comparison of the LSC expression data to that of normal hematopoietic stem cells (HSC) revealed that 34% of the modulated genes are shared by both LSC and HSC, supporting the suggestion that the LSC originated within the HSC progenitors. We focused on the Notch pathway since Jagged-2, a Notch ligand was found to be overexpressed in the LSC samples. We show that DAPT, an inhibitor of gamma-secretase, a protease that is involved in Jagged and Notch signaling, inhibits LSC growth in colony formation assays. Identification of additional genes that regulate LSC self-renewal may provide new targets for therapy.


systematic_name: M14877
exact_source: Table 1S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in SKOC-3 cells (ovarian cancer) after YB-1 (YBX1) [GeneID=4904] knockdown by RNAi.

description_full:
  Y-box-binding protein 1 (YB-1), which is a member of the DNA-binding protein family containing a cold-shock domain, has pleiotropic functions in response to various environmental stimuli. As we previously showed that YB-1 is a global marker of multidrug resistance in ovarian cancer and other tumor types. To identify YB-1-regulated genes in ovarian cancers, we investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. YB-1 knockdown by siRNA upregulated 344 genes, including MDR1, thymidylate synthetase, S100 calcium binding protein and cyclin B, and downregulated 534 genes, including CXCR4, N-myc downstream regulated gene 1, E-cadherin and phospholipase C. Exogenous serum addition stimulated YB-1 translocation from the cytoplasm to the nucleus, and treatment with Akt inhibitors as well as Akt siRNA and integrin-linked kinase (ILK) siRNA specifically blocked YB-1 nuclear localization. Inhibition of Akt activation downregulated CXCR4 and upregulated MDR1 (ABCB1) gene expression. Administration of Akt inhibitor resulted in decrease in nuclear YB-1-positive cancer cells in a xenograft animal model. Akt activation thus regulates the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. Therefore, the Akt pathway could be a novel target of disrupting the nuclear translocation of YB-1 that has important implications for further development of therapeutic strategy against ovarian cancers.


systematic_name: M15927
exact_source: Table 2S: Direction=D
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in HCT8/S1 cells (colon cancer) which normally lack DCC [GeneID=9423] compared to those stably expressing wild type DCC off a plasmid vector.

description_full:
[cell repeats an earlier one in this file: 1687 characters]


systematic_name: M4735
exact_source: Figure 6S
source_species_code: HS
GEO_id: GSE7382
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in MCF7 cells (breast cancer) engineered to conditionally express LMO4 [GeneID=8543] by a Tet Off system.

description_full:
  The nuclear LIM-only protein 4 (LMO4) is upregulated in breast cancer, especially estrogen receptor-negative tumors, and its overexpression in mice leads to hyperplasia and tumor formation. Here, we show that deletion of LMO4 in the mammary glands of mice leads to impaired lobuloalveolar development due to decreased epithelial cell proliferation. With the goal of discovering potential LMO4-target genes, we also developed a conditional expression system in MCF-7 cells for both LMO4 and a dominant negative (DN) form of its co-regulator, cofactor of LIM domains (Clim/Ldb/Nli). We then used DNA microarrays to identify genes responsive to LMO4 and DN-Clim upregulation. One of the genes common to both data sets was bone morphogenic protein 7 (BMP7), whose expression is also significantly correlated with LMO4 transcript levels in a large dataset of human breast cancers, suggesting that BMP7 is a bona fide target gene of LMO4 in breast cancer. Inhibition of BMP7 partially blocks the effects of LMO4 on apoptosis, indicating that BMP7 mediates at least some functions of LMO4. Gene transfer studies show that LMO4 regulates the BMP7 promoter, and chromatin immunoprecipitation studies show that LMO4 and its cofactor Clim2 are recruited to the BMP7 promoter. Furthermore, we demonstrate that HDAC2 recruitment to the BMP7 promoter is inhibited by upregulation of LMO4 and that HDAC2 knockdown upregulates the promoter. These studies suggest a novel mechanism of action for LMO4: LMO4, Clim2 and HDAC2 are part of a transcriptional complex, and increased LMO4 levels can disrupt the complex, leading to decreased HDAC2 recruitment and increased promoter activity.


systematic_name: M10334
exact_source: Figure 7S
source_species_code: HS
GEO_id: GSE7382
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in MCF7 cells (breast cancer) engineered to conditionally express a dominant negative form of CLIM2 [GeneID=8861] by a Tet Off system.

description_full:
[cell repeats an earlier one in this file: 1668 characters]


systematic_name: M17079
exact_source: Table 2S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Up-regulated genes distinguishing between two subtypes of gastric cancer: advanced (AGC) and early (EGC).

description_full:
  Gastric carcinoma is one of the major causes of cancer mortality worldwide. Early detection results in excellent prognosis for patients with early cancer (EGC), whereas the prognosis of advanced cancer (AGC) patients remains poor. It is not clear whether EGC and AGC are molecularly distinct, and whether they represent progressive stages of the same tumor or different entities ab initio. Gene expression profiles of EGC and AGC were determined by Affymetrix technology and quantitative polymerase chain reaction. Representative regulated genes were further analysed by in situ hybridization (ISH) on tissue microarrays. Expression analysis allowed the identification of a signature that differentiates AGC from EGC. In addition, comparison with normal gastric mucosa indicated that the majority of alterations associated with EGC are retained in AGC, and that further expression changes mark the transition from EGC to AGC. Finally, ISH analysis showed that representative genes, differentially expressed in the invasive areas of EGC and AGC, are not differentially expressed in the non-invasive areas of the same tumors. Our data are more directly compatible with a progression model of gastric carcinogenesis, whereby EGC and AGC may represent different molecular stages of the same tumor. Finally, the identification of an AGC-specific signature might help devising novel therapeutic strategies for advanced gastric cancer.


systematic_name: M986
exact_source: Table 1BS: Log2 Ratio Mean(Cancer/Normal) > 0
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in circulating endothelial cells (CEC) from cancer patients compared to those from healthy donors.

description_full:
  Increased numbers of endothelial cells are observed in peripheral blood of cancer patients. These circulating endothelial cells (CECs) may contribute to the formation of blood vessels in the tumor or reflect vascular damage caused by treatment or tumor growth. Characterization of these cells may aid in the understanding of the angiogenic process and may provide biomarkers for treatment efficacy of angiogenesis inhibitors. To identify markers typical for CECs in cancer patients, we assessed global gene expression profiles of CD146 immunomagnetically enriched CECs from healthy donors and patients with metastatic breast, colorectal, prostate, lung, and renal cancer. From the generated gene profiles, a list of 61 marker genes for CEC detection was generated, and their expression was measured by real-time quantitative PCR in blood samples from 81 metastatic cancer patients and 55 healthy donors that were immunomagnetically enriched for CECs. A set of 34 genes, among which novel CEC-associated genes, such as THBD, BST1, TIE1, POSTN1, SELE, SORT1, and DTR, were identified that were expressed at higher levels in cancer patients compared with healthy donors. Expression of the VWF, DTR, CDH5, TIE, and IGFBP7 genes were found to discriminate between cancer patients and healthy donors with a receiver operating characteristic curve accuracy of 0.93. Assessment of the expression of these genes may provide biomarkers to evaluate treatment efficacy.


description_brief: Genes up-regulated in blood samples from bladder cancer patients.
systematic_name: M5275
exact_source: Table 1S
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_full:
  PURPOSE: Recent data indicate that cDNA microarray gene expression profile of blood cells can reflect disease states and thus have diagnostic value. We tested the hypothesis that blood cell gene expression can differentiate between bladder cancer and other genitourinary cancers as well as between bladder cancer and healthy controls. EXPERIMENTAL DESIGN: We used Affymetrix U133 Plus 2.0 GeneChip (Affymetrix, Santa Clara, CA) to profile circulating blood total RNA from 35 patients diagnosed with one of three types of genitourinary cancer [bladder cancer (n = 16), testicular cancer (n = 10), and renal cell carcinoma (n = 9)] and compared their cDNA profiles with those of 10 healthy subjects. We then verified the expression levels of selected genes from the Affymetrix results in a larger number of bladder cancer patients (n = 40) and healthy controls (n = 27). RESULTS: Blood gene expression profiles distinguished bladder cancer patients from healthy controls and from testicular and renal cancer patients. Differential expression of a combined set of seven gene transcripts (insulin-like growth factor-binding protein 7, sorting nexin 16, chondroitin sulfate proteoglycan 6, and cathepsin D, chromodomain helicase DNA-binding protein 2, nell-like 2, and tumor necrosis factor receptor superfamily member 7) was able to discriminate bladder cancer from control samples with a sensitivity of 83% (95% confidence interval, 67-93%) and a specificity of 93% (95% confidence interval, 76-99%). CONCLUSION: We have shown that the gene expression profile of circulating blood cells can distinguish bladder cancer from other types of genitourinary cancer and healthy controls and can be used to identify novel blood markers for bladder cancer.


systematic_name: M7089
exact_source: supplementdown.pdf
source_species_code: HS
GEO_id: GSE3003
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in hematopoietic stem cells (HSC, CD34+ [GeneID=947]) cultured in a three-dimentional collagen gel compared to the cells grown in suspension.

description_full:
  CD34+ hematopoietic stem/progenitor cells (HSCs) reside in the bone marrow in close proximity to the endosteal bone surface, surrounded by osteoblasts, stromal cells, and various extracellular matrix molecules. We used a bioartificial matrix of fibrillar collagen I, the major matrix component of bone, as a scaffold for ex vivo expansion of HSCs. CD34+ HSCs were isolated from umbilical cord blood and cultivated within reconstituted collagen I fibrils in the presence of fms-like tyrosine kinase-3 ligand, stem cell factor, and interleukin (IL)-3. After 7 days of culture, the cell number, number of colony-forming units (CFU-C), and gene-expression profile of the cultured cells were assessed. Although the total expansion factor of CD34+ cells was slightly lower when cells were cultivated in the collagen I gel, the frequency of CFU-C was greater than in control suspension cultures. Gene-expression analysis with microarray chip technology revealed the upregulation of more than 50 genes in the presence of collagen I. Among these, genes for several growth factors, cytokines, and chemokines (e.g., IL-8 and macrophage inhibitory protein 1alpha) could be confirmed using quantitative polymerase chain reaction. Furthermore, greater expression levels of the negative cell-cycle regulator BTG2/TIS21 and an inhibitor of the mitogen-activated protein kinase pathway, DUSP2, underline the regulatory role of the extracellular matrix. Together, these data show that the expansion of CD34+ cord blood cells in a culture system containing a three-dimensional collagen I matrix induces a qualitative change in the gene-expression profile of cultivated HSCs.


systematic_name: M11672
exact_source: Table 1S: module=blue & fold change >= 1.5
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes from the blue module which are up-regulated in HAEC cells (primary aortic endothelium) after exposure to the oxidized 1-palmitoyl-2-arachidonyl-sn-3-glycerophosphorylcholine (oxPAPC).

description_full:
[cell repeats an earlier one in this file: 1667 characters]


systematic_name: M9740
exact_source: Table 3S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in CD34+ [GeneID=947] hematopoetic cells by expression of NUP98-HOXA9 fusion [GeneID=4928;3205] off a retroviral vector at 8 days after transduction.

description_full:
  NUP98-HOXA9, the chimeric protein resulting from the t(7;11)(p15;p15) chromosomal translocation, is a prototype of several NUP98 fusions that occur in myelodysplastic syndromes and acute myeloid leukemia. We examined its effect on differentiation, proliferation, and gene expression in primary human CD34+ hematopoietic cells. Colony-forming cell (CFC) assays in semisolid medium combined with morphologic examination and flow cytometric immunophenotyping revealed that NUP98-HOXA9 increased the numbers of erythroid precursors and impaired both myeloid and erythroid differentiation. In continuous liquid culture, cells transduced with NUP98-HOXA9 exhibited a biphasic growth curve with initial growth inhibition followed by enhanced long-term proliferation, suggesting an increase in the numbers of primitive self-renewing cells. This was confirmed by a dramatic increase in the numbers of long-term culture-initiating cells, the most primitive hematopoietic cells detectable in vitro. To understand the molecular mechanisms underlying the effects of NUP98-HOXA9 on hematopoietic cell proliferation and differentiation, oligonucleotide microarray analysis was done at several time points over 16 days, starting at 6 hours posttransduction. The early growth suppression was preceded by up-regulation of IFNbeta1 and accompanied by marked up-regulation of IFN-induced genes, peaking at 3 days posttransduction. In contrast, oncogenes such as homeobox transcription factors, FLT3, KIT, and WT1 peaked at 8 days or beyond, coinciding with increased proliferation. In addition, several putative tumor suppressors and genes associated with hematopoietic differentiation were repressed at later time points. These findings provide a comprehensive picture of the changes in proliferation, differentiation, and global gene expression that underlie the leukemic transformation of human hematopoietic cells by NUP98-HOXA9.


systematic_name: M7388
exact_source: Table 4S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in CD34+ [GeneID=947] hematopoetic cells by expression of NUP98-HOXA9 fusion [GeneID=4928;3205] off a retroviral vector at 10 days after transduction.

description_full:
[cell repeats an earlier one in this file: 1913 characters]


systematic_name: M15410
exact_source: Table 5S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in CD34+ [GeneID=947] hematopoetic cells by expression of NUP98-HOXA9 fusion [GeneID=4928;3205] off a retroviral vector at 16 days after transduction.

description_full:
[cell repeats an earlier one in this file: 1913 characters]


systematic_name: M1859
exact_source: Table 3S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in ALL (acute lymphoblastic leukemia) blasts after 1 week of treatment with glucocorticoids.

description_full:
  In childhood acute lymphoblastic leukemia (ALL), persistence of leukemic blasts during therapy is of crucial prognostic significance. In the present study, we address molecular and cell biologic features of blasts persisting after 1 week of induction glucocorticoid therapy. Genome-wide gene expression analysis of leukemic samples from precursor B-cell ALL patients (n=18) identified a set of genes differentially expressed in blasts at diagnosis day 0 (d0) and persisting on day 8 (d8). Expression changes indicate a shift towards mature B cells, inhibition of cell cycling and increased expression of adhesion (CD11b/ITGAM) and cytokine (CD119/IFNGR1) receptors. A direct comparison with normal B cells, which are largely therapy resistant, confirmed the differentiation shift at the mRNA (n=10) and protein (n=109) levels. Flow cytometric analysis in independent cohorts of patients confirmed both a decreased proliferative activity (n=13) and the upregulation of CD11b and CD119 (n=29) in d8 blasts. The differentiation shift and low proliferative activity in d8 blasts may account for the persistence of blasts during therapy and affect their sensitivity to further therapeutic treatment. CD11b and CD119 are potential specific markers for d8 blast persistence and detection of minimal residual disease, which warrant further investigation.


description_brief: Genes up-regulated in U2OS cells (osteosarcoma) upon knockdown of HDAC1 [GeneID=3065] by RNAi.
systematic_name: M14973
exact_source: Table 1S: HDAC1=U
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_full:
  Posttranslational modifications of core histones are central to the regulation of gene expression. Histone deacetylases (HDACs) repress transcription by deacetylating histones, and class I HDACs have a crucial role in mouse, Xenopus laevis, zebra fish, and Caenorhabditis elegans development. The role of individual class I HDACs in tumor cell proliferation was investigated using RNA interference-mediated protein knockdown. We show here that in the absence of HDAC1 cells can arrest either at the G(1) phase of the cell cycle or at the G(2)/M transition, resulting in the loss of mitotic cells, cell growth inhibition, and an increase in the percentage of apoptotic cells. On the contrary, HDAC2 knockdown showed no effect on cell proliferation unless we concurrently knocked down HDAC1. Using gene expression profiling analysis, we found that inactivation of HDAC1 affected the transcription of specific target genes involved in proliferation and apoptosis. Furthermore, HDAC2 downregulation did not cause significant changes compared to control cells, while inactivation of HDAC1, HDAC1 plus HDAC2, or HDAC3 resulted in more distinct clusters. Loss of these HDACs might impair cell cycle progression by affecting not only the transcription of specific target genes but also other biological processes. Our data support the idea that a drug targeting specific HDACs could be highly beneficial in the treatment of cancer.


systematic_name: M18938
exact_source: Table 1S: HDAC1+2=U
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in U2OS cells (osteosarcoma) upon knockdown of both HDAC1 and HDAC2 [GeneID=3065;3066] by RNAi.

description_full:
  Posttranslational modifications of core histones are central to the regulation of gene expression. Histone deacetylases (HDACs) repress transcription by deacetylating histones, and class I HDACs have a crucial role in mouse, Xenopus laevis, zebra fish, and Caenorhabditis elegans development. The role of individual class I HDACs in tumor cell proliferation was investigated using RNA interference-mediated protein knockdown. We show here that in the absence of HDAC1 cells can arrest either at the G(1) phase of the cell cycle or at the G(2)/M transition, resulting in the loss of mitotic cells, cell growth inhibition, and an increase in the percentage of apoptotic cells. On the contrary, HDAC2 knockdown showed no effect on cell proliferation unless we concurrently knocked down HDAC1. Using gene expression profiling analysis, we found that inactivation of HDAC1 affected the transcription of specific target genes involved in proliferation and apoptosis. Furthermore, HDAC2 downregulation did not cause significant changes compared to control cells, while inactivation of HDAC1, HDAC1 plus HDAC2, or HDAC3 resulted in more distinct clusters. Loss of these HDACs might impair cell cycle progression by affecting not only the transcription of specific target genes but also other biological processes. Our data support the idea that a drug targeting specific HDACs could be highly beneficial in the treatment of cancer.


systematic_name: M12004
exact_source: Table 1S: HDAC1+2=D
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in U2OS cells (osteosarcoma) upon knockdown of both HDAC1 and HDAC2 [GeneID=3065;3066] by RNAi.

description_full:
[cell repeats an earlier one in this file: 1423 characters]


systematic_name: M8916
exact_source: Table 1S: 2h coculture
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in Caco-2 cells (intestinal epithelium) after coculture with the probiotic bacteria L. casei for 2h.

description_full:
  Shigella invades the human intestinal mucosa, thus causing bacillary dysentery, an acute recto-colitis responsible for lethal complications, mostly in infants and toddlers. Conversely, commensal bacteria live in a mutualistic relationship with the intestinal mucosa that is characterized by homeostatic control of innate responses, thereby contributing to tolerance to the flora. Cross-talk established between commensals and the intestinal epithelium mediate this active process, the mechanisms of which remain largely uncharacterized. Probiotics such as Lactobacillus casei belong to a subclass of these commensals that modulate mucosal innate responses and possibly display anti-inflammatory properties. We analyzed whether L. casei could attenuate the pro-inflammatory signaling induced by Shigella flexneri after invasion of the epithelial lining. Cultured epithelial cells were infected with L. casei, followed by a challenge with S. flexneri. Using macroarray DNA chips, we observed that L. casei down-regulated the transcription of a number of genes encoding pro-inflammatory effectors such as cytokines and chemokines and adherence molecules induced by invasive S. flexneri. This resulted in an anti-inflammatory effect that appeared mediated by the inhibition of the NF-kappaB pathway, particularly through stabilization of I-kappaBalpha. In a time-course experiment using GeneChip hybridization analysis, the expression of many genes involved in ubiquitination and proteasome processes were modulated during L. casei treatment. Thus, L. casei has developed a sophisticated means to maintain intestinal homeostasis through a process that involves manipulation of the ubiquitin/proteasome pathway upstream of I-kappaBalpha.


systematic_name: M19990
exact_source: Table 1S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in Caco-2 cells (intestinal epithelium) after coculture with the probiotic bacteria L. casei for 6h.

description_full:
  Shigella invades the human intestinal mucosa, thus causing bacillary dysentery, an acute recto-colitis responsible for lethal complications, mostly in infants and toddlers. Conversely, commensal bacteria live in a mutualistic relationship with the intestinal mucosa that is characterized by homeostatic control of innate responses, thereby contributing to tolerance to the flora. Cross-talk established between commensals and the intestinal epithelium mediate this active process, the mechanisms of which remain largely uncharacterized. Probiotics such as Lactobacillus casei belong to a subclass of these commensals that modulate mucosal innate responses and possibly display anti-inflammatory properties. We analyzed whether L. casei could attenuate the pro-inflammatory signaling induced by Shigella flexneri after invasion of the epithelial lining. Cultured epithelial cells were infected with L. casei, followed by a challenge with S. flexneri. Using macroarray DNA chips, we observed that L. casei down-regulated the transcription of a number of genes encoding pro-inflammatory effectors such as cytokines and chemokines and adherence molecules induced by invasive S. flexneri. This resulted in an anti-inflammatory effect that appeared mediated by the inhibition of the NF-kappaB pathway, particularly through stabilization of I-kappaBalpha. In a time-course experiment using GeneChip hybridization analysis, the expression of many genes involved in ubiquitination and proteasome processes were modulated during L. casei treatment. Thus, L. casei has developed a sophisticated means to maintain intestinal homeostasis through a process that involves manipulation of the ubiquitin/proteasome pathway upstream of I-kappaBalpha.


systematic_name: M1463
exact_source: Table 1S: 24h coculture
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in Caco-2 cells (intestinal epithelium) after coculture with the probiotic bacteria L. casei for 24h.

description_full:
  Shigella invades the human intestinal mucosa, thus causing bacillary dysentery, an acute recto-colitis responsible for lethal complications, mostly in infants and toddlers. Conversely, commensal bacteria live in a mutualistic relationship with the intestinal mucosa that is characterized by homeostatic control of innate responses, thereby contributing to tolerance to the flora. Cross-talk established between commensals and the intestinal epithelium mediate this active process, the mechanisms of which remain largely uncharacterized. Probiotics such as Lactobacillus casei belong to a subclass of these commensals that modulate mucosal innate responses and possibly display anti-inflammatory properties. We analyzed whether L. casei could attenuate the pro-inflammatory signaling induced by Shigella flexneri after invasion of the epithelial lining. Cultured epithelial cells were infected with L. casei, followed by a challenge with S. flexneri. Using macroarray DNA chips, we observed that L. casei down-regulated the transcription of a number of genes encoding pro-inflammatory effectors such as cytokines and chemokines and adherence molecules induced by invasive S. flexneri. This resulted in an anti-inflammatory effect that appeared mediated by the inhibition of the NF-kappaB pathway, particularly through stabilization of I-kappaBalpha. In a time-course experiment using GeneChip hybridization analysis, the expression of many genes involved in ubiquitination and proteasome processes were modulated during L. casei treatment. Thus, L. casei has developed a sophisticated means to maintain intestinal homeostasis through a process that involves manipulation of the ubiquitin/proteasome pathway upstream of I-kappaBalpha.


systematic_name: M80
exact_source: Suppl. Data 2: 1610 EWSFLI upregulated genes
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in TC71 and EWS502 cells (Ewing's sarcoma) by EWSR1-FLI1  [GeneID=2130;2314] as inferred from RNAi knockdown of this fusion protein.

description_full:
  A number of solid tumors, such as alveolar rhabdomyosarcoma, synovial sarcoma, and myxoid liposarcoma, are associated with recurrent translocation events that encode fusion proteins. Ewing's sarcoma is a pediatric tumor that serves as a prototype for this tumor class. Ewing's sarcomas usually harbor the (11;22)(q24;q12) translocation. The t(11;22) encodes the EWS/FLI fusion oncoprotein. EWS/FLI functions as an aberrant transcription factor, but the key target genes that are involved in oncogenesis are largely unknown. Although some target genes have been defined, many of these have been identified in heterologous model systems with uncertain relevance to the human disease. To understand the function of EWS/FLI and its targets in a more clinically relevant system, we used retroviral-mediated RNAi to knock-down the fusion protein in patient-derived Ewing's sarcoma cell lines. By combining transcriptional profiling data from three of these lines, we identified a conserved transcriptional response to EWS/FLI. The gene that was most reproducibly up-regulated by EWS/FLI was NR0B1. NR0B1 is a developmentally important orphan nuclear receptor with no previously defined role in oncogenesis. We validated NR0B1 as an EWS/FLI-dysregulated gene and confirmed its expression in primary human tumor samples. Functional studies revealed that ongoing NR0B1 expression is required for the transformed phenotype of Ewing's sarcoma. These studies define a new role for NR0B1 in oncogenic transformation and emphasize the utility of analyzing the function of EWS/FLI in Ewing's sarcoma cells.


systematic_name: M13206
exact_source: Suppl. Data 2: 436 EWSFLI downregulated genes
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in TC71 and EWS502 cells (Ewing's sarcoma) by EWSR1-FLI1  [GeneID=2130;2314] as inferred from RNAi knockdown of this fusion protein.

description_full:
  A number of solid tumors, such as alveolar rhabdomyosarcoma, synovial sarcoma, and myxoid liposarcoma, are associated with recurrent translocation events that encode fusion proteins. Ewing's sarcoma is a pediatric tumor that serves as a prototype for this tumor class. Ewing's sarcomas usually harbor the (11;22)(q24;q12) translocation. The t(11;22) encodes the EWS/FLI fusion oncoprotein. EWS/FLI functions as an aberrant transcription factor, but the key target genes that are involved in oncogenesis are largely unknown. Although some target genes have been defined, many of these have been identified in heterologous model systems with uncertain relevance to the human disease. To understand the function of EWS/FLI and its targets in a more clinically relevant system, we used retroviral-mediated RNAi to knock-down the fusion protein in patient-derived Ewing's sarcoma cell lines. By combining transcriptional profiling data from three of these lines, we identified a conserved transcriptional response to EWS/FLI. The gene that was most reproducibly up-regulated by EWS/FLI was NR0B1. NR0B1 is a developmentally important orphan nuclear receptor with no previously defined role in oncogenesis. We validated NR0B1 as an EWS/FLI-dysregulated gene and confirmed its expression in primary human tumor samples. Functional studies revealed that ongoing NR0B1 expression is required for the transformed phenotype of Ewing's sarcoma. These studies define a new role for NR0B1 in oncogenic transformation and emphasize the utility of analyzing the function of EWS/FLI in Ewing's sarcoma cells.


systematic_name: M17859
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE5117
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in UB27 cells (osteosarcoma) at any time point after inducing the expression of a mutant form of WT1 [GeneID=7490].

description_full:
  The Wilms' tumor suppressor gene (WT1) encodes a zinc finger transcription factor that is vital during development of several organs including metanephric kidneys. Despite the critical regulatory role of WT1, the pathways and mechanisms by which WT1 orchestrates development remain elusive. To identify WT1 target genes, we performed a genome-wide expression profiling analysis in cells expressing inducible WT1. We identified a number of direct WT1 target genes, including the epidermal growth factor (EGF)-family ligands epiregulin and HB-EGF, the chemokine CX3CL1, and the transcription factors SLUG and JUNB. The target genes were validated using quantitative reverse transcriptase-polymerase chain reaction, small interfering RNA knockdowns, chromatin immunoprecipitation, and luciferase reporter analyses. Immunohistochemistry of fetal kidneys confirmed that a number of the WT1 target genes had overlapping expression patterns with the highly restricted spatiotemporal expression of WT1. Finally, using an in vitro embryonic kidney culture assay, we found that the addition of recombinant epiregulin, amphiregulin, CX3CL1, and interleukin-11 significantly enhanced ureteric bud branching morphogenesis. Our genome-wide screen implicates WT1 in the transcriptional regulation of the EGF-family of growth factors as well as the CX3CL1 chemokine during nephrogenesis.


systematic_name: M9948
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE5117
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in UB27 cells (osteosarcoma) at 8 hr after inducing the expression of a mutant form of WT1 [GeneID=7490].

description_full:
  The Wilms' tumor suppressor gene (WT1) encodes a zinc finger transcription factor that is vital during development of several organs including metanephric kidneys. Despite the critical regulatory role of WT1, the pathways and mechanisms by which WT1 orchestrates development remain elusive. To identify WT1 target genes, we performed a genome-wide expression profiling analysis in cells expressing inducible WT1. We identified a number of direct WT1 target genes, including the epidermal growth factor (EGF)-family ligands epiregulin and HB-EGF, the chemokine CX3CL1, and the transcription factors SLUG and JUNB. The target genes were validated using quantitative reverse transcriptase-polymerase chain reaction, small interfering RNA knockdowns, chromatin immunoprecipitation, and luciferase reporter analyses. Immunohistochemistry of fetal kidneys confirmed that a number of the WT1 target genes had overlapping expression patterns with the highly restricted spatiotemporal expression of WT1. Finally, using an in vitro embryonic kidney culture assay, we found that the addition of recombinant epiregulin, amphiregulin, CX3CL1, and interleukin-11 significantly enhanced ureteric bud branching morphogenesis. Our genome-wide screen implicates WT1 in the transcriptional regulation of the EGF-family of growth factors as well as the CX3CL1 chemokine during nephrogenesis.


systematic_name: M4987
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE5117
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in UB27 cells (osteosarcoma) at 12 hr after inducing the expression of a mutated form of WT1 [GeneID=7490].

description_full:
  The Wilms' tumor suppressor gene (WT1) encodes a zinc finger transcription factor that is vital during development of several organs including metanephric kidneys. Despite the critical regulatory role of WT1, the pathways and mechanisms by which WT1 orchestrates development remain elusive. To identify WT1 target genes, we performed a genome-wide expression profiling analysis in cells expressing inducible WT1. We identified a number of direct WT1 target genes, including the epidermal growth factor (EGF)-family ligands epiregulin and HB-EGF, the chemokine CX3CL1, and the transcription factors SLUG and JUNB. The target genes were validated using quantitative reverse transcriptase-polymerase chain reaction, small interfering RNA knockdowns, chromatin immunoprecipitation, and luciferase reporter analyses. Immunohistochemistry of fetal kidneys confirmed that a number of the WT1 target genes had overlapping expression patterns with the highly restricted spatiotemporal expression of WT1. Finally, using an in vitro embryonic kidney culture assay, we found that the addition of recombinant epiregulin, amphiregulin, CX3CL1, and interleukin-11 significantly enhanced ureteric bud branching morphogenesis. Our genome-wide screen implicates WT1 in the transcriptional regulation of the EGF-family of growth factors as well as the CX3CL1 chemokine during nephrogenesis.


systematic_name: M6905
exact_source: Table 2S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in CD133+ [GeneID=8842] cells (hematopoietic stem cells, HSC) compared to the CD133- cells.

description_full:
  Human cord blood (CB)-derived CD133+ cells carry characteristics of primitive hematopoietic cells and proffer an alternative for CD34+ cells in hematopoietic stem cell (HSC) transplantation. To characterize the CD133+ cell population on a genetic level, a global expression analysis of CD133+ cells was performed using oligonucleotide microarrays. CD133+ cells were purified from four fresh CB units by immunomagnetic selection. All four CD133+ samples showed significant similarity in their gene expression pattern, whereas they differed clearly from the CD133- control samples. In all, 690 transcripts were differentially expressed between CD133+ and CD133- cells. Of these, 393 were increased and 297 were decreased in CD133+ cells. The highest overexpression was noted in genes associated with metabolism, cellular physiological processes, cell communication, and development. A set of 257 transcripts expressed solely in the CD133+ cell population was identified. Colony-forming unit (CFU) assay was used to detect the clonal progeny of precursors present in the studied cell populations. The results demonstrate that CD133+ cells express primitive markers and possess clonogenic progenitor capacity. This study provides a gene expression profile for human CD133+ cells. It presents a set of genes that may be used to unravel the properties of the CD133+ cell population, assumed to be highly enriched in HSCs.


systematic_name: M10501
exact_source: Table 1S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in poorly differentiated thyroid carcinoma (PDTC) compared to normal thyroid tissue.

description_full:
  Information on gene alterations associated to poorly differentiated (PDTC) and anaplastic thyroid carcinomas (ATC) is scarce. Using human cancer cell lines as a tool for gene discovery, we performed a cytogenetic and oligo-array analysis in five new cell lines derived from two PDTC and three ATC. In PDTC we evidenced, as important, the involvement of the MAPK/ERK kinase pathway, and downregulation of a group of suppressor genes that include E-cadherin. In ATC, downregulation of a specific group of oncosuppressor genes was also observed. Our ATC cell lines presented chromosomal markers of gene amplification, and we were able to identify for the first time the nature of the involved amplicon target genes. We found that the main molecular differences between the two cell line types were related to signal transduction pathways, cell adhesion and motility process. TaqMan experiments performed for five amplicon target genes and for two genes, which allowed a clear distinction between ATC and PDTC: CDH13 and PLAU corroborated array results, not only in the cell lines, but also in an additional set of primary 14 PDTC and three ATC. We suggest that our findings may represent new tools for the development of more effective therapies to the hitherto untreatable ATC.


systematic_name: M16651
exact_source: Table 1S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in poorly differentiated thyroid carcinoma (PDTC) compared to normal thyroid tissue.

description_full:
[cell repeats an earlier one in this file: 1275 characters]


systematic_name: M10961
exact_source: Table 1S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in TMX2-28 cells (breast cancer) which do not express ESR1 [GeneID=2099]) compared to the parental MCF7 cells which do.

description_full:
  We have used a novel variant of the human oestrogen receptor (ER)-positive MCF-7 cell line, TMX2-28, as a model to study breast cancer. TMX2-28 cells show no detectable levels of mRNA or protein expression for the ER and express basal cytokeratins (CKs) 5, 14, and 17. cDNA microarray comparison between TMX2-28 and its parent cell line, MCF-7, identified 1402 differentially expressed transcripts, one of which was, phospholipase D1 (PLD1). Using real-time RT-PCR, we confirmed that PLD1 mRNA levels are 10-fold higher in TMX2-28 cells than in MCF-7 cells. We next examined PLD1 expression in human breast carcinomas. Phospholipase D1 mRNA levels were higher in breast tumours that expressed high-mRNA levels of basal CKs 5 and/or 17, but PLD1 mRNA levels were not significantly higher in ER-negative tumours. Phospholipase D1 protein was overexpressed in 10 of 42 (24%) breast tumours examined by IHC. Phospholipase D1 was overexpressed in 6 of 31 ER-positive tumours and 4 of 11 ER-negative tumours. Phospholipase D1 was overexpressed in three of the four tumours that showed high CK5/17 expression. Five PLD1-positive tumours were negative for phospho-Akt expression, but positive for phospho-mammalian target of rapamycin (mTOR) expression. The other five PLD1-positive breast tumours showed positive expression for phospho-Akt; however, only two of these cases were positive for phospho-mTOR. In this study, we report that PLD1 and phospho-mTOR are coexpressed in a subset of phospho-Akt-negative breast carcinomas.


systematic_name: M6564
exact_source: Table 4S: M >= 1
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in lesional skin biopsies from mycosis fundoides patients compared to the normal skin samples.

description_full:
[cell repeats an earlier one in this file: 1743 characters]


systematic_name: M9016
exact_source: Table 3S: FC < -1
source_species_code: HS
GEO_id: GSE2509,GSE1323
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in polysomal and total RNA samples from SW480 cells (primary colorectal carcinoma, CRC) compared to the SW620 cells (lymph node metastasis from the same individual).

description_full:
  Tumour onset and progression are due to the accumulation of genomic lesions, which alter gene expression and ultimately proteome activities. These lesions are thought to affect primarily the transcriptional control of gene expression. In the present study, we aimed at evaluating the genome-wide occurrence of alterations in the translational control exploiting an isogenic, phenotypically validated cellular model of colorectal cancer (CRC) transition from invasive carcinoma to metastasis. In this model, microarray profiling shows that changes in the level of messenger ribonucleic acid (mRNA) association with polysomes occur more than 2-fold than changes in the level of total cellular mRNA. When common to both the total and polysomal compartments, these changes are also homodirectional, being amplified in magnitude at the polysomal level. Comparison between the transcriptional and the translational fluctuations revealed distinct signatures of statistically over-represented gene functions, involving the program of cell proliferation for both levels of analysis, while the apoptosis and the translation programs were affected mainly at translation. Looking for an upstream determinant of translational deregulation, we found an increase in the hyperphosphorylated form of the 4E-BP1 protein in the metastatic cell line, possibly resulting in an increased activation of cap-dependent translation due to increased activity of the eIF4E protein. Analysis of the distribution profiles for the 5' untranslated region (5'-UTR) length of the changed genes showed an association between longer 5'-UTRs and the probability for the relevant gene to be altered translationally, consistent with enhanced eIF4E function. This genome-wide analysis is in favour of a model of profound alteration of translational control in late CRC progression. It also suggests polysomal mRNA profiles as a new, informative dimension for the study of transcriptome imbalance in cancer.


description_brief: Genes up-regulated in epidermis after to UVB irradiation.
systematic_name: M19848
exact_source: Table 1S
source_species_code: HS
contributor: Lauren Kazmierski
contrib_organization: MSigDB Team
description_full:
  In order to obtain a comprehensive picture of the molecular events regulating cutaneous photodamage of intact human epidermis, suction blister roofs obtained after a single dose of in vivo ultraviolet (UV)B exposure were used for microarray profiling. We found a changed expression of 619 genes. Half of the UVB-regulated genes had returned to pre-exposure baseline levels at 72 h, underscoring the transient character of the molecular cutaneous UVB response. Of special interest was our finding that several of the central p53 target genes remained unaffected following UVB exposure in spite of p53 protein accumulation. We next compared the in vivo expression profiles of epidermal sheets to that of cultured human epidermal keratinocytes exposed to UVB in vitro. We found 1931 genes that differed in their expression profiles between the two groups. The expression profile in intact epidemis was geared mainly towards DNA repair, whereas cultured keratinocytes responded predominantly by activating genes associated with cell-cycle arrest and apoptosis. These differences in expression profiles might reflect differences between mature differentiating keratinocytes in the suprabasal epidermal layers versus exponentially proliferating keratinocytes in cell culture. Our findings show that extreme care should be taken when extrapolating from findings based on keratinocyte cultures to changes in intact epidermis.


description_brief: Genes up-regulated in papillary thyroid carcinoma (PTC) compared to normal tissue.
systematic_name: M3645
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE3950
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  The purpose of this paper is to correlate the molecular phenotype of papillary thyroid carcinoma (PTC) to their biological pathology. We hybridized 26 PTC on microarrays and showed that nearly 44% of the transcriptome was regulated in these tumors. We then combined our data set with two published PTC microarray studies to produce a platform- and study-independent list of PTC-associated genes. We further confirmed the mRNA regulation of 15 genes from this list by quantitative reverse transcription-PCR. Analysis of this list with statistical tools led to several conclusions: (1) there is a change in cell population with an increased expression of genes involved in the immune response, reflecting lymphocyte infiltration in the tumor compared to the normal tissue. (2) The c-jun N-terminal kinase pathway is activated by overexpression of its components. (3) The activation of ERKK1/2 by genetic alterations is supplemented by activation of the epidermal growth factor but not of the insulin-like growth factor signaling pathway. (4) There is a downregulation of immediate early genes. (5) We observed an overexpression of many proteases in accordance with tumor remodeling, and suggested a probable role of S100 proteins and annexin A2 in this process. (6) Numerous overexpressed genes favor the hypothesis of a collective migration mode of tumor cells.


systematic_name: M4716
exact_source: Table 1S
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in SH-SY5Y cells (neuroblastoma) after treatment with epoxomicin [PubChem=3035402], a protease inhibitor causing apoptosis.

description_full:
  The proteasome has emerged as a novel target for antineoplastic treatment of hematological malignancies and solid tumors, including those of the central nervous system. To identify cell death pathways activated in response to inhibition of the proteasome system in cancer cells, we treated human SH-SY5Y neuroblastoma cells with the selective proteasome inhibitor (PI) epoxomicin (Epoxo). Prolonged exposure to Epoxo was associated with increased levels of poly-ubiquitinylated proteins and p53, release of cytochrome c from the mitochondria, and activation of caspases. Analysis of global gene expression using high-density oligonucleotide microarrays revealed that Epoxo triggered transcriptional activation of the two Bcl-2-homology domain-3-only (BH3-only) genes p53 upregulated modulator of apoptosis (PUMA) and Bim. Subsequent studies in PUMA- and Bim-deficient cells indicated that Epoxo-induced caspase activation and apoptosis was predominantly PUMA-dependent. Further characterization of the transcriptional response to Epoxo in HCT116 human colon cancer cells demonstrated that PUMA induction was p53-dependent; with deficiency in either p53 or PUMA significantly protected HCT116 cells against Epoxo-induced apoptosis. Our data suggest that p53 activation and the transcriptional induction of its target gene PUMA play an important role in the sensitivity of cancer cells to apoptosis induced by proteasome inhibition, and imply that antineoplastic therapies with PIs might be especially useful in cancers with functional p53.


systematic_name: M12272
exact_source: Table 1S
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in PaCa44 and CFPAC1 cells (pancreatic cancer) after treatment with decitabine [PubChem=451668], a DNA hypomethylating agent similar to azacitidine [PubChem=9444].

description_full:
  Alteration of methylation status has been recognized as a possible epigenetic mechanism of selection during tumorigenesis in pancreatic cancer. This type of cancer is characterized by poor prognosis partly due to resistance to conventional drug treatments. We have used microarray technology to investigate the changes in global gene expression observed after treatment of different pancreatic cancer cell lines with the methylase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR). We have observed that this agent is able to inhibit to various degrees the growth of three pancreatic cancer cell lines. In particular, this inhibition was associated with induction of interferon (IFN)-related genes, as observed in other tumour types. Thus, expression of STAT1 seems to play a key role in the cellular response to treatment with the cytosine analogue. Moreover, we found increased p21(WAF1) and gadd45A expression to be associated with the efficacy of the treatment; this induction may correlate with activation of the IFN signalling pathway. Expression of the p16(INK) protein was also linked to the ability of cells to respond to 5-aza-CdR. Finally, genome-wide demethylation induced sensitization that significantly increased response to further treatment with various chemotherapy agents.


systematic_name: M18979
exact_source: Table 5S
source_species_code: HS
GEO_id: E-MEXP-247
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in T1 cells (primary melanoma, sensitive to TRAIL [GeneID=8743]) compared to G1 cells (metastatic melanoma, resistant to TRAIL).

description_full:
  In order to define genetic determinants of primary and metastatic melanoma cell susceptibility to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we have applied oligonucleotide microarrays to TRAIL-sensitive primary T1 cells and TRAIL-resistant metastatic G1 cells treated or not with TRAIL. T1 and G1 cells are isogenic melanoma cell subclones. We examined 22 000 spots, 4.2% of which displayed differential expression in G1 and T1 cells. Cell susceptibility to TRAIL-mediated apoptosis was found to be correlated with gene expression signatures in this model. Some of the differentially expressed genes were identified as involved in ATP-binding and signaling pathways, based on previously published data. Further analysis provided evidences that c-kit was overexpressed in G1 cells while it was absent in T1 cells. The c-kit inhibitor, imatinib, did not restore TRAIL sensitivity, excluding a role for c-kit in TRAIL resistance in G1 cells. Surprisingly, imatinib inhibited cell proliferation and TRAIL-mediated apoptosis in melanoma cells. We investigated the possible involvement of several molecules, including c-ABL, platelet-derived growth factor receptor (PDGFR), cellular FADD-like interleukin-1 alpha-converting enzyme-like inhibitory protein (c-FLIP)(L/S), Fas-associated DD kinase, p53, p21(WAF1), proteins of B-cell leukemia/lymphoma 2 (Bcl-2) family and cytochrome c. Imatinib did not modulate the expression or activation of its own targets, such as c-ABL, PDGFRalpha and PDGFRbeta, but it did affect the expression of c-FLIP(L), BCL2-associated X protein (Bax) and Bcl-2. Moreover, c-FLIP(L) knockdown sensitized T1 cells to TRAIL-mediated apoptosis, with a sensitivity similar to that of cells previously treated with imatinib. More notably, we found that the resistance to TRAIL in G1 cells was correlated with constitutive c-FLIP(L) recruitment to the DISC and the inhibition of caspase 8, 3 and 9 processing. Moreover, c-FLIP(L) knockdown partly restored TRAIL sensitivity in G1 cells, indicating that the expression level of c-FLIP(L) and its interaction with TRAIL receptor2 play a crucial role in determining TRAIL resistance in metastatic melanoma cells. Our results also show that imatinib enhances TRAIL-induced cell death independently of BH3-interacting domain death agonist translocation, in a process involving the Bax:Bcl-X(L) ratio, Bax:Bcl-X(L)/Bcl-2 translocation, cytochrome c release and caspase activation. Our data indicate that imatinib sensitizes T1 cells by directly downregulating c-FLIP(L), with the use of an alternative pathway for antitumor activity, because PDGFRalpha is not activated in T1 cells and these cells do not express c-kit, c-ABL or PDGFRbeta. Caspase cascade activation and mitochondria also play a key role in the imatinib-mediated sensitization of melanoma cells to the proapoptotic action of TRAIL.


systematic_name: M15912
exact_source: Table 6S
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in T1 cells (primary melanoma, sensitive to TRAIL [GeneID=8743]) compared to G1 cells (metastatic melanoma, resistant to TRAIL).

description_full:
  In order to define genetic determinants of primary and metastatic melanoma cell susceptibility to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we have applied oligonucleotide microarrays to TRAIL-sensitive primary T1 cells and TRAIL-resistant metastatic G1 cells treated or not with TRAIL. T1 and G1 cells are isogenic melanoma cell subclones. We examined 22 000 spots, 4.2% of which displayed differential expression in G1 and T1 cells. Cell susceptibility to TRAIL-mediated apoptosis was found to be correlated with gene expression signatures in this model. Some of the differentially expressed genes were identified as involved in ATP-binding and signaling pathways, based on previously published data. Further analysis provided evidences that c-kit was overexpressed in G1 cells while it was absent in T1 cells. The c-kit inhibitor, imatinib, did not restore TRAIL sensitivity, excluding a role for c-kit in TRAIL resistance in G1 cells. Surprisingly, imatinib inhibited cell proliferation and TRAIL-mediated apoptosis in melanoma cells. We investigated the possible involvement of several molecules, including c-ABL, platelet-derived growth factor receptor (PDGFR), cellular FADD-like interleukin-1 alpha-converting enzyme-like inhibitory protein (c-FLIP)(L/S), Fas-associated DD kinase, p53, p21(WAF1), proteins of B-cell leukemia/lymphoma 2 (Bcl-2) family and cytochrome c. Imatinib did not modulate the expression or activation of its own targets, such as c-ABL, PDGFRalpha and PDGFRbeta, but it did affect the expression of c-FLIP(L), BCL2-associated X protein (Bax) and Bcl-2. Moreover, c-FLIP(L) knockdown sensitized T1 cells to TRAIL-mediated apoptosis, with a sensitivity similar to that of cells previously treated with imatinib. More notably, we found that the resistance to TRAIL in G1 cells was correlated with constitutive c-FLIP(L) recruitment to the DISC and the inhibition of caspase 8, 3 and 9 processing. Moreover, c-FLIP(L) knockdown partly restored TRAIL sensitivity in G1 cells, indicating that the expression level of c-FLIP(L) and its interaction with TRAIL receptor2 play a crucial role in determining TRAIL resistance in metastatic melanoma cells. Our results also show that imatinib enhances TRAIL-induced cell death independently of BH3-interacting domain death agonist translocation, in a process involving the Bax:Bcl-X(L) ratio, Bax:Bcl-X(L)/Bcl-2 translocation, cytochrome c release and caspase activation. Our data indicate that imatinib sensitizes T1 cells by directly downregulating c-FLIP(L), with the use of an alternative pathway for antitumor activity, because PDGFRalpha is not activated in T1 cells and these cells do not express c-kit, c-ABL or PDGFRbeta. Caspase cascade activation and mitochondria also play a key role in the imatinib-mediated sensitization of melanoma cells to the proapoptotic action of TRAIL.


systematic_name: M1784
exact_source: Table 1S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes changed in U373-MG cells (malignant glioma) upon treatment with arsenic trioxide [PubChem=14888], a chemical that can cause autophagic cell death.

description_full:
  Arsenic trioxide (As(2)O(3)) has shown considerable efficacy in treating hematological malignancies with induction of programmed cell death (PCD) type I, apoptosis. However, the mechanisms underlying the antitumor effect of As(2)O(3) on solid tumors are poorly defined. Previously, we reported that As(2)O(3) induced autophagic cell death (PCD type II) but not apoptosis in human malignant glioma cell lines. The purpose of this study was to elucidate the molecular pathway leading to autophagic cell death. In this study, we demonstrated that the cell death was accompanied by involvement of autophagy-specific marker, microtubule-associated protein light chain 3 (LC3), and damage of mitochondrial membrane integrity, but not by caspase activation. Analysis by cDNA microarray, RT-PCR, and Western blot showed that cell death members of Bcl-2 family, Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) and its homologue BNIP3-like (BNIP3L), were upregulated in As(2)O(3)-induced autophagic cell death. Exogenous expression of BNIP3, but not BNIP3L, induced autophagic cell death in malignant glioma cells without As(2)O(3) treatment. When upregulation of BNIP3 induced by As(2)O(3) was suppressed by a dominant-negative effect of the transmembrane-deleted BNIP3 (BNIP3 Delta TM), autophagic cell death was inhibited. In contrast, BNIP3 transfection augmented As(2)O(3)-induced autophagic cell death. These results suggest that BNIP3 plays a central role in As(2)O(3)-induced autophagic cell death in malignant glioma cells. This study adds a new concept to characterize the pathways by which As(2)O(3) acts to induce autophagic cell death in malignant glioma cells.


description_brief: Genes up-regulated in short-term cultured glioblastomas after azacitidine [PubChem=9444] treatment.
systematic_name: M912
exact_source: Table 3S
source_species_code: HS
GEO_id: GSE4717
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_full:
  Glioblastoma, the most aggressive and least treatable form of malignant glioma, is the most common human brain tumor. Although many regions of allelic loss occur in glioblastomas, relatively few tumor suppressor genes have been found mutated at such loci. To address the possibility that epigenetic alterations are an alternative means of glioblastoma gene inactivation, we coupled pharmacological manipulation of methylation with gene profiling to identify potential methylation-regulated, tumor-related genes. Duplicates of three short-term cultured glioblastomas were exposed to 5 microM 5-aza-dC for 96 h followed by cRNA hybridization to an oligonucleotide microarray (Affymetrix U133A). We based candidate gene selection on bioinformatics, reverse transcription-polymerase chain reaction (RT-PCR), bisulfite sequencing, methylation-specific PCR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Two genes identified in this manner, RUNX3 and Testin (TES), were subsequently shown to harbor frequent tumor-specific epigenetic alterations in primary glioblastomas. This overall approach therefore provides a powerful means to identify candidate tumor-suppressor genes for subsequent evaluation and may lead to the identification of genes whose epigenetic dysregulation is integral to glioblastoma tumorigenesis.


systematic_name: M1410
exact_source: Table 4S
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Cluster 4: genes down-regulated in B493-6 cells (B lymphocytes) upon serum stimulation but not affected by MYC [GeneID=4609].

description_full:
[cell repeats an earlier one in this file: 1496 characters]


description_brief: Genes up-regulated in hepatocellular carcinoma (HCC) compared to normal liver samples.
systematic_name: M1195
exact_source: Suppl. file 4
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Hepatocellular carcinoma (HCC) is one of the major causes of cancer deaths worldwide. New diagnostic and therapeutic options are needed for more effective and early detection and treatment of this malignancy. We identified 703 genes that are highly expressed in HCC using DNA microarrays, and further characterized them in order to uncover novel tumor markers, oncogenes, and therapeutic targets for HCC. Using Gene Ontology annotations, genes with functions related to cell proliferation and cell cycle, chromatin, repair, and transcription were found to be significantly enriched in this list of highly expressed genes. We also identified a set of genes that encode secreted (e.g. GPC3, LCN2, and DKK1) or membrane-bound proteins (e.g. GPC3, IGSF1, and PSK-1), which may be attractive candidates for the diagnosis of HCC. A significant enrichment of genes highly expressed in HCC was found on chromosomes 1q, 6p, 8q, and 20q, and we also identified chromosomal clusters of genes highly expressed in HCC. The microarray analyses were validated by RT-PCR and PCR. This approach of integrating other biological information with gene expression in the analysis helps select aberrantly expressed genes in HCC that may be further studied for their diagnostic or therapeutic utility.


systematic_name: M4500
exact_source: Table 1S: CC = D & SLR <= -1 in at least one condition
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in fibroblasts expressing mutant forms of ERCC3 [GeneID=2071] after UV irradiation.

description_full:
[cell repeats an earlier one in this file: 1438 characters]


systematic_name: M13522
exact_source: Table 3S, 2S: common down-regulated
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Common down-regulated transcripts in fibroblasts expressing either XP/CS or TDD mutant forms of ERCC3 [GeneID=2071], after UVC irradiation.

description_full:
[cell repeats an earlier one in this file: 1438 characters]


description_brief: Genes discriminating responses to sodium arsenite [PubChem=26435] from other stresses.
systematic_name: M262
exact_source: Table 5S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Gene expression responses of human cell lines exposed to a diverse set of stress agents were compared by cDNA microarray hybridization. The B-lymphoblastoid cell line TK6 (p53 wild-type) and its p53-null derivative, NH32, were treated in parallel to facilitate investigation of p53-dependent responses. RNA was extracted 4 h after the beginning of treatment when no notable decrease in cell viability was evident in the cultures. Gene expression signatures were defined that discriminated between four broad general mechanisms of stress agents: Non-DNA-damaging stresses (heat shock, osmotic shock, and 12-O-tetradecanoylphorbol 13-acetate), agents causing mainly oxidative stress (arsenite and hydrogen peroxide), ionizing radiations (neutron and gamma-ray exposures), and other DNA-damaging agents (ultraviolet radiation, methyl methanesulfonate, adriamycin, camptothecin, and cis-Platinum(II)diammine dichloride (cisplatin)). Within this data set, non-DNA-damaging stresses could be discriminated from all DNA-damaging stresses, and profiles for individual agents were also defined. While DNA-damaging stresses showed a strong p53-dependent element in their responses, no discernible p53-dependent responses were triggered by the non-DNA-damaging stresses. A set of 16 genes did exhibit a robust p53-dependent pattern of induction in response to all nine DNA-damaging agents, however.


description_brief: Genes up-regulated between two breast carcinoma subtypes: metaplastic (MCB) and ductal (DCB).
systematic_name: M15975
exact_source: Table 1S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Metaplastic carcinoma of the breast (MCB) is a poorly understood subtype of breast cancer. It is generally characterized by the coexistence of ductal carcinomatous and transdifferentiated sarcomatous components, but the underlying molecular alterations, possibly related to epithelial-mesenchymal transition (EMT), remain elusive. We performed transcriptional profiling using half-a-genome oligonucleotide microarrays to elucidate genetic profiles of MCBs and their differences to those of ductal carcinoma of breasts (DCBs) using discarded specimens of four MCBs and 34 DCBs. Unsupervised clustering disclosed distinctive expression profiles between MCBs and DCBs. Supervised analysis identified gene signatures discriminating MCBs from DCBs and between MCB subclasses. Notably, many of the discriminator genes were associated with downregulation of epithelial phenotypes and with synthesis, remodeling and adhesion of extracellular matrix, with some of them have known or inferred roles related to EMT. Importantly, several of the discriminator genes were upregulated in a mutant Snail-transfected MCF7 cell known to exhibit features of EMT, thereby indicating a crucial role for EMT in the pathogenesis of MCBs. Finally, the identification of SPARC and vimentin as poor prognostic factors reinforced the role of EMT in cancer progression. These data advance our understanding of MCB and offer clues to the molecular alterations underlying EMT.


systematic_name: M15193
exact_source: Table 1S: FC > 1
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in pancreatic ductal adenocarcinoma (PDAC) identified in a meta analysis across four independent studies.

description_full:
  Pancreatic ductal adenocarcinoma is the eighth most common cancer with the lowest overall 5-year relative survival rate of any tumor type today. Expression profiling using microarrays has been widely used to identify genes associated with pancreatic cancer development. To extract maximum value from the available gene expression data, we applied a meta-analysis to search for commonly differentially expressed genes in pancreatic ductal adenocarcinoma. We obtained data sets from four different gene expression studies on pancreatic cancer. We selected a consensus set of 2984 genes measured in all four studies and applied a meta-analysis approach to evaluate the combined data. Of the genes identified as differentially expressed, several were validated using RT-PCR and immunohistochemistry. Additionally, we used a class discovery algorithm to identify a gene expression signature. Our meta-analysis revealed that the pancreatic cancer gene expression data sets shared a significant number of up- and downregulated genes, independent of the technology used. This interstudy crossvalidation approach generated a set of 568 genes that were consistently and significantly dysregulated in pancreatic cancer. Of these, 364 (64.1%) were upregulated and 204 (35.9%) were downregulated in pancreatic cancer. Only 127 (22%) were described in the published individual analyses. Functional annotation of the genes revealed that genes presumably associated with the cell adhesion-mediated drug resistance pathway are frequently overexpressed in pancreatic cancer. Meta-analysis is an important tool for the identification and validation of differentially expressed genes. These could represent good candidates for novel diagnostic and therapeutic approaches to pancreatic cancer.


systematic_name: M10431
exact_source: Table 1S: FC < 1
source_species_code: HS
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in pancreatic ductal adenocarcinoma (PDAC) identified in a meta analysis across four independent studies.

description_full:
  Pancreatic ductal adenocarcinoma is the eighth most common cancer with the lowest overall 5-year relative survival rate of any tumor type today. Expression profiling using microarrays has been widely used to identify genes associated with pancreatic cancer development. To extract maximum value from the available gene expression data, we applied a meta-analysis to search for commonly differentially expressed genes in pancreatic ductal adenocarcinoma. We obtained data sets from four different gene expression studies on pancreatic cancer. We selected a consensus set of 2984 genes measured in all four studies and applied a meta-analysis approach to evaluate the combined data. Of the genes identified as differentially expressed, several were validated using RT-PCR and immunohistochemistry. Additionally, we used a class discovery algorithm to identify a gene expression signature. Our meta-analysis revealed that the pancreatic cancer gene expression data sets shared a significant number of up- and downregulated genes, independent of the technology used. This interstudy crossvalidation approach generated a set of 568 genes that were consistently and significantly dysregulated in pancreatic cancer. Of these, 364 (64.1%) were upregulated and 204 (35.9%) were downregulated in pancreatic cancer. Only 127 (22%) were described in the published individual analyses. Functional annotation of the genes revealed that genes presumably associated with the cell adhesion-mediated drug resistance pathway are frequently overexpressed in pancreatic cancer. Meta-analysis is an important tool for the identification and validation of differentially expressed genes. These could represent good candidates for novel diagnostic and therapeutic approaches to pancreatic cancer.


systematic_name: M6998
exact_source: Table 1AS
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in PCI-35 cells (pancreatic cancer, lack endogenous DUSP6 [GeneID=1848]) upon expression of DUSP6 off an adenoviral vector.

description_full:
  DUSP6/MKP-3, a specific inhibitor of MAPK1/ERK2, frequently loses its expression in primary pancreatic cancer tissues. This evidence suggests that constitutive activation of MAPK1 synergistically induced by frequent mutation of KRAS2 and the loss of function of DUSP6 plays key roles in pancreatic carcinogenesis and progression. By profiling of gene expressions associated with downregulation of MAPK1 induced by exogenous overexpression of DUSP6 in pancreatic cancer cells, we found that AURKA/STK15, the gene encoding Aurora-A kinase, which plays key roles in cellular mitosis, was among the downregulated genes along with its related genes, which included AURKB, TPX2 and CENPA. An association of expression and promoter activity of AURKA with MAPK activity was verified. Knockdown of ETS2 resulted in a reduction of AURKA expression. These results indicate that AURKA is a direct target of the MAPK pathway and that its overexpression in pancreatic cancer is induced by hyperactivation of the pathway, at least via ETS2.


systematic_name: M14665
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE5859
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in lymphoblastoid cells from the European population compared to those from the Asian population.

description_full:
  Variation in DNA sequence contributes to individual differences in quantitative traits, but in humans the specific sequence variants are known for very few traits. We characterized variation in gene expression in cells from individuals belonging to three major population groups. This quantitative phenotype differs significantly between European-derived and Asian-derived populations for 1,097 of 4,197 genes tested. For the phenotypes with the strongest evidence of cis determinants, most of the variation is due to allele frequency differences at cis-linked regulators. The results show that specific genetic variation among populations contributes appreciably to differences in gene expression phenotypes. Populations differ in prevalence of many complex genetic diseases, such as diabetes and cardiovascular disease. As some of these are probably influenced by the level of gene expression, our results suggest that allele frequency differences at regulatory polymorphisms also account for some population differences in prevalence of complex diseases.


systematic_name: M16066
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE5859
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in lymphoblastoid cells from the European population compared to those from the Asian population.

description_full:
[cell repeats an earlier one in this file: 1057 characters]


systematic_name: M5611
exact_source: Table 2S: BRCA1-PCCs
source_species_code: HS
GEO_id: GSE6534
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes constituting the BRCA1-PCC network of transcripts whose expression positively correlated (Pearson correlation coefficient, PCC >= 0.4) with that of BRCA1 [GeneID=672] across a compendium of normal tissues.

description_full:
  Many cancer-associated genes remain to be identified to clarify the underlying molecular mechanisms of cancer susceptibility and progression. Better understanding is also required of how mutations in cancer genes affect their products in the context of complex cellular networks. Here we have used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. Starting with four known genes encoding tumor suppressors of breast cancer, we combined gene expression profiling with functional genomic and proteomic (or 'omic') data from various species to generate a network containing 118 genes linked by 866 potential functional associations. This network shows higher connectivity than expected by chance, suggesting that its components function in biologically related pathways. One of the components of the network is HMMR, encoding a centrosome subunit, for which we demonstrate previously unknown functional associations with the breast cancer-associated gene BRCA1. Two case-control studies of incident breast cancer indicate that the HMMR locus is associated with higher risk of breast cancer in humans. Our network modeling strategy should be useful for the discovery of additional cancer-associated genes.


systematic_name: M9585
exact_source: Table 2S: ATM-PCCs
source_species_code: HS
GEO_id: GSE6534
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes constituting the ATM-PCC network of transcripts whose expression positively correlated (Pearson correlation coefficient, PCC >= 0.4) with that of ATM [GeneID=472] across a compendium of normal tissues.

description_full:
  Many cancer-associated genes remain to be identified to clarify the underlying molecular mechanisms of cancer susceptibility and progression. Better understanding is also required of how mutations in cancer genes affect their products in the context of complex cellular networks. Here we have used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. Starting with four known genes encoding tumor suppressors of breast cancer, we combined gene expression profiling with functional genomic and proteomic (or 'omic') data from various species to generate a network containing 118 genes linked by 866 potential functional associations. This network shows higher connectivity than expected by chance, suggesting that its components function in biologically related pathways. One of the components of the network is HMMR, encoding a centrosome subunit, for which we demonstrate previously unknown functional associations with the breast cancer-associated gene BRCA1. Two case-control studies of incident breast cancer indicate that the HMMR locus is associated with higher risk of breast cancer in humans. Our network modeling strategy should be useful for the discovery of additional cancer-associated genes.


systematic_name: M11961
exact_source: Table 2S: CHEK2-PCCs
source_species_code: HS
GEO_id: GSE6534
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes constituting the CHEK2-PCC network of transcripts whose expression positively correlates (Pearson correlation coefficient, PCC >= 0.4) with that of CHEK2 [GeneID=11200].

description_full:
[cell repeats an earlier one in this file: 1255 characters]


description_brief: Genes up-regulated in PC3 cells (prostate cancer) after knockdown of NIPP1 [GeneID=5511] by RNAi.
systematic_name: M6444
exact_source: Table 1S
source_species_code: HS
GEO_id: E-TABM-128
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_full:
  EZH2 is a Polycomb group (PcG) protein that promotes the late-stage development of cancer by silencing a specific set of genes, at least in part through trimethylation of associated histone H3 on Lys 27 (H3K27). Nuclear inhibitor of protein phosphatase-1 (NIPP1) is a ubiquitously expressed transcriptional repressor that has binding sites for the EZH2 interactor EED. Here, we examine the contribution of NIPP1 to EZH2-mediated gene silencing. Studies on NIPP1-deficient cells disclose a widespread and essential role of NIPP1 in the trimethylation of H3K27 by EZH2, not only in the onset of this trimethylation during embryonic development, but also in the maintenance of this repressive mark in proliferating cells. Consistent with this notion, EZH2 and NIPP1 silence a common set of genes, as revealed by gene-expression profiling, and NIPP1 is associated with established Polycomb target genes and with genomic regions that are enriched in Polycomb targets. Furthermore, most NIPP1 target genes are trimethylated on H3K27 and the knockdown of either NIPP1 or EZH2 is often associated with a loss of this modification. Our data reveal that NIPP1 is required for the global trimethylation of H3K27 and is implicated in gene silencing by EZH2.


systematic_name: M6782
exact_source: Table 1S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in T24 (bladder cancer) cells in response to the photodynamic therapy (PDT) stress.

description_full:
  Photodynamic therapy (PDT) is an anticancer approach utilizing a light-absorbing molecule and visible light irradiation to generate, in the presence of O(2), cytotoxic reactive oxygen species, which cause tumor ablation. Given that the photosensitizer hypericin is under consideration for PDT treatment of bladder cancer we used oligonucleotide microarrays in the T24 bladder cancer cell line to identify differentially expressed genes with therapeutic potential. This study reveals that the expression of several genes involved in various metabolic processes, stress-induced cell death, autophagy, proliferation, inflammation and carcinogenesis is strongly affected by PDT and pinpoints the coordinated induction of a cluster of genes involved in the unfolded protein response pathway after endoplasmic reticulum stress and in antioxidant response. Analysis of PDT-treated cells after p38(MAPK) inhibition or silencing unraveled that the induction of an important subset of differentially expressed genes regulating growth and invasion, as well as adaptive mechanisms against oxidative stress, is governed by this stress-activated kinase. Moreover, p38(MAPK) inhibition blocked autonomous regrowth and migration of cancer cells escaping PDT-induced cell death. This analysis identifies new molecular effectors of the cancer cell response to PDT opening attractive avenues to improve the therapeutic efficacy of hypericin-based PDT of bladder cancer.


systematic_name: M10351
exact_source: Table 2S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in T24 (bladder cancer) cells in response to the photodynamic therapy (PDT) stress.

description_full:
  Photodynamic therapy (PDT) is an anticancer approach utilizing a light-absorbing molecule and visible light irradiation to generate, in the presence of O(2), cytotoxic reactive oxygen species, which cause tumor ablation. Given that the photosensitizer hypericin is under consideration for PDT treatment of bladder cancer we used oligonucleotide microarrays in the T24 bladder cancer cell line to identify differentially expressed genes with therapeutic potential. This study reveals that the expression of several genes involved in various metabolic processes, stress-induced cell death, autophagy, proliferation, inflammation and carcinogenesis is strongly affected by PDT and pinpoints the coordinated induction of a cluster of genes involved in the unfolded protein response pathway after endoplasmic reticulum stress and in antioxidant response. Analysis of PDT-treated cells after p38(MAPK) inhibition or silencing unraveled that the induction of an important subset of differentially expressed genes regulating growth and invasion, as well as adaptive mechanisms against oxidative stress, is governed by this stress-activated kinase. Moreover, p38(MAPK) inhibition blocked autonomous regrowth and migration of cancer cells escaping PDT-induced cell death. This analysis identifies new molecular effectors of the cancer cell response to PDT opening attractive avenues to improve the therapeutic efficacy of hypericin-based PDT of bladder cancer.


systematic_name: M4120
exact_source: Table 1S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in HeLa cells (cervical cancer) after simultaneus knockdown of all three MBD (methyl-CpG binding domain) proteins MeCP2, MBD1 and MBD2 [GeneID=4204;4152;8932] by RNAi.

description_full:
  Methyl-cytosine-phosphate-guanine (CpG)-binding domain (MBD) proteins are bound to hypermethylated promoter CpG islands of tumor suppressor genes in human cancer cells, although a direct causal relationship at the genome-wide level between MBD presence and gene silencing remains to be demonstrated. To this end, we have inhibited the expression of MBD proteins in HeLa cells by short hairpin RNAs; and studied the functional consequences of MBD depletion using microarray-based expression analysis in conjunction with extensive bisulfite genomic sequencing and chromatin immunoprecipitation. The removal of MBDs results in a release of gene silencing associated with a loss of MBD occupancy in 5'-CpG islands without any change in the DNA methylation pattern. Our results unveil new targets for epigenetic inactivation mediated by MBDs in transformed cells, such as the cell adhesion protein gamma-parvin and the fibroblast growth factor 19, where we also demonstrate their bona fide tumor suppressor features. Our data support a fundamental role for MBD proteins in the direct maintenance of transcriptional repression of tumor suppressors and identify new candidate genes for epigenetic disruption in cancer cells.


systematic_name: M12113
exact_source: Table 4S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes whose promoters contain E-box motifs and whose expression changed in MYCN-3 cells (neuroblastoma) upon induction of MYCN [GeneID=4613].

description_full:
  Loss of 1p36 heterozygosity commonly occurs with MYCN amplification in neuroblastoma tumors, and both are associated with an aggressive phenotype. Database searches identified five microRNAs that map to the commonly deleted region of 1p36 and we hypothesized that the loss of one or more of these microRNAs contributes to the malignant phenotype of MYCN-amplified tumors. By bioinformatic analysis, we identified that three out of the five microRNAs target MYCN and of these miR-34a caused the most significant suppression of cell growth through increased apoptosis and decreased DNA synthesis in neuroblastoma cell lines with MYCN amplification. Quantitative RT-PCR showed that neuroblastoma tumors with 1p36 loss expressed lower level of miR-34a than those with normal copies of 1p36. Furthermore, we demonstrated that MYCN is a direct target of miR-34a. Finally, using a series of mRNA expression profiling experiments, we identified other potential direct targets of miR-34a, and pathway analysis demonstrated that miR-34a suppresses cell-cycle genes and induces several neural-related genes. This study demonstrates one important regulatory role of miR-34a in cell growth and MYCN suppression in neuroblastoma.


systematic_name: M12369
exact_source: Table 7S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in metastatic vs non-metastatic HNSCC (head and neck squamous cell carcinoma) samples.

description_full:
[cell repeats an earlier one in this file: 1435 characters]


systematic_name: M12746
exact_source: Table 1S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in NCI-H1299 cells (large cell neuroendocrine carcinoma) stably expressing SEMA3B [GeneID=7869].

description_full:
  SEMA3B, a member of class 3 semaphorins, is a tumor suppressor. Competition with vascular endothelial growth factor (VEGF)165 explains a portion of the activity, whereas the VEGF-independent mechanism was not elucidated. We employed a microarray and screened for the genes whose expression was increased by SEMA3B in NCI-H1299 cells. Insulin-like growth factor-binding protein-6 (IGFBP-6), a tumor suppressor, showed greatest difference in the expression level. Introduction of IGFBP-6 cDNA reduced colony formation both on the dish surface and in soft agar. Insulin-like growth factor II, which antagonizes IGFBP-6, partly abrogated the effect. Inhibition of IGFBP-6 by small interfering RNA diminished the sub-G0/G1 population that was induced by SEMA3B and abrogated the growth suppressive effect of SEMA3B. We concluded that IGFBP-6 is the effector of tumor suppressor activity of SEMA3B in NCI-H1299 cells. It has been reported that beta-catenin suppresses the expression of IGFBP-6. Introduction of beta-catenin into the cells partly abrogated the growth suppressive effect of SEMA3B. Our result indicates that semaphorin signaling and beta-catenin signaling converge on IGFBP-6 and antithetically affect their functions.


systematic_name: M2029
exact_source: Table 2S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in NCI-H1299 cells (large cell neuroendocrine carcinoma) stably expressing SEMA3B [GeneID=7869].

description_full:
  SEMA3B, a member of class 3 semaphorins, is a tumor suppressor. Competition with vascular endothelial growth factor (VEGF)165 explains a portion of the activity, whereas the VEGF-independent mechanism was not elucidated. We employed a microarray and screened for the genes whose expression was increased by SEMA3B in NCI-H1299 cells. Insulin-like growth factor-binding protein-6 (IGFBP-6), a tumor suppressor, showed greatest difference in the expression level. Introduction of IGFBP-6 cDNA reduced colony formation both on the dish surface and in soft agar. Insulin-like growth factor II, which antagonizes IGFBP-6, partly abrogated the effect. Inhibition of IGFBP-6 by small interfering RNA diminished the sub-G0/G1 population that was induced by SEMA3B and abrogated the growth suppressive effect of SEMA3B. We concluded that IGFBP-6 is the effector of tumor suppressor activity of SEMA3B in NCI-H1299 cells. It has been reported that beta-catenin suppresses the expression of IGFBP-6. Introduction of beta-catenin into the cells partly abrogated the growth suppressive effect of SEMA3B. Our result indicates that semaphorin signaling and beta-catenin signaling converge on IGFBP-6 and antithetically affect their functions.


systematic_name: M1871
exact_source: Table 1S: ES exp1
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Set 'ES exp1': genes overexpressed in human embryonic stem cells according to 5 or more out of 20 profiling studies.

description_full:
[cell repeats an earlier one in this file: 1354 characters]


systematic_name: M6616
exact_source: Table 1S: Nanog targets
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Set 'Nanog targets': genes upregulated and identified by ChIP on chip as Nanog [GeneID=79923] transcription factor targets in human embryonic stem cells.

description_full:
[cell repeats an earlier one in this file: 1354 characters]


systematic_name: M17183
exact_source: Table 1S: Oct4 targets
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Set 'Oct4 targets': genes upregulated and identified by ChIP on chip as OCT4 [GeneID=5460] transcription factor targets in human embryonic stem cells.

description_full:
[cell repeats an earlier one in this file: 1354 characters]


systematic_name: M3835
exact_source: Table 1S: Sox2 targets
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Set 'Sox2 targets': genes upregulated and identified by ChIP on chip as SOX2 [GeneID=6657] transcription factor targets in human embryonic stem cells.

description_full:
[cell repeats an earlier one in this file: 1354 characters]


systematic_name: M14573
exact_source: Table 1S: NOS targets
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Set 'NOS targets': genes upregulated and identified by ChIP on chip as targets of the transcription factors NANOG , OCT4, and Sox2 [GeneID=79923;5460;6657] (NOS) in human embryonic stem cells.

description_full:
[cell repeats an earlier one in this file: 1354 characters]


systematic_name: M27
exact_source: Table 1S: Myc targets1
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Set 'Myc targets1': targets of c-Myc [GeneID=4609] identified by ChIP on chip in cultured cell lines, focusing on E-box-containing genes; high affinity bound subset

description_full:
[cell repeats an earlier one in this file: 1354 characters]


systematic_name: M17753
exact_source: Table 1S: Myc targets2
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Set 'Myc targets2': targets of c-Myc [GeneID=4609] and Max [GeneID=4149] identified by ChIP on chip in a Burkitt's lymphoma cell line; overlap set.

description_full:
[cell repeats an earlier one in this file: 1354 characters]


systematic_name: M18120
exact_source: Table ES
source_species_code: HS
GEO_id: GSE13105
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in HCT116 cells (colon cancer) by expression of MIR192 or MIR215 [GeneID=406967;406997] at 24 h.

description_full:
  Cell cycle arrest in response to DNA damage is an important antitumorigenic mechanism. MicroRNAs (miRNAs) were recently shown to play key regulatory roles in cell cycle progression. For example, miR-34a is induced in response to p53 activation and mediates G(1) arrest by down-regulating multiple cell cycle-related transcripts. Here we show that genotoxic stress promotes the p53-dependent up-regulation of the homologous miRNAs miR-192 and miR-215. Like miR-34a, activation of miR-192/215 induces cell cycle arrest, suggesting that multiple miRNA families operate in the p53 network. Furthermore, we define a downstream gene expression signature for miR-192/215 expression, which includes a number of transcripts that regulate G(1) and G(2) checkpoints. Of these transcripts, 18 transcripts are direct targets of miR-192/215, and the observed cell cycle arrest likely results from a cooperative effect among the modulations of these genes by the miRNAs. Our results showing a role for miR-192/215 in cell proliferation combined with recent observations that these miRNAs are underexpressed in primary cancers support the idea that miR-192 and miR-215 function as tumor suppressors.


systematic_name: M29
exact_source: Fig S6: correlated
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes whose expression positively correlated with that of SMARCA2 [GeneID=6595] in prostate cancer samples.

description_full:
  Factors that drive prostate cancer progression remain poorly defined, thus hindering the development of new therapeutic strategies. Disseminated tumors are treated through regimens that ablate androgen signaling, as prostate cancer cells require androgen for growth and survival. However, recurrent, incurable tumors that have bypassed the androgen requirement ultimately arise. This study reveals that the Brm ATPase, a component of selected SWI/SNF complexes, has significant antiproliferative functions in the prostate that protect against these transitions. First, we show that targeted ablation of Brm is causative for the development of prostatic hyperplasia in mice. Second, in vivo challenge revealed that Brm-/- epithelia acquire the capacity for lobe-specific, castration-resistant cellular proliferation. Third, investigation of human specimens revealed that Brm mRNA and protein levels are attenuated in prostate cancer. Fourth, Brm down-regulation was associated with an increased proliferative index, consistent with the mouse model. Lastly, gene expression profiling showed that Brm loss alters factors upstream of E2F1; this was confirmed in murine models, wherein Brm loss induced E2F1 deregulation in a tissue-specific manner. Combined, these data identify Brm as a major effector of serum androgen-induced proliferation in the prostate that is disrupted in human disease, and indicate that loss of Brm confers a proliferative advantage in prostate cancer.


systematic_name: M13867
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE9691
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in HMLE cells (immortalized nontransformed mammary epithelium) after E-cadhedrin (CDH1) [GeneID=999] knockdown by RNAi.

description_full:
[cell repeats an earlier one in this file: 1076 characters]


systematic_name: M15484
exact_source: Table 4S
source_species_code: HS
GEO_id: GSE9691
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes changed in HMLE cells (mmortalized nontransformed mammary epithelium) after RNAi knockdown of both CDH1 and CTNNB1 [GeneID=999;1499], compared to the knockdown of CDH1 alone.

description_full:
[cell repeats an earlier one in this file: 1076 characters]


systematic_name: M17742
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE361
contributor: Pablo Tamayo
contrib_organization: MSigDB Team
description_brief:
  Genes consistently up-regulated in HMEC cells (primary mammary epithelium) upon expression of TERT [GeneID=7015] off a retroviral vector.

description_full:
  Most somatic cells do not express sufficient amounts of telomerase to maintain a constant telomere length during cycles of chromosome replication. Consequently, there is a limit to the number of doublings somatic cells can undergo before telomere shortening triggers an irreversible state of cellular senescence. Ectopic expression of telomerase overcomes this limitation, and in conjunction with specific oncogenes can transform cells to a tumorigenic phenotype. However, recent studies have questioned whether the stabilization of chromosome ends entirely explains the ability of telomerase to promote tumorigenesis and have resulted in the hypothesis that telomerase has a second function that also supports cell division. Here we show that ectopic expression of telomerase in human mammary epithelial cells (HMECs) results in a diminished requirement for exogenous mitogens and that this correlates with telomerase-dependent induction of genes that promote cell growth. Furthermore, we show that inhibiting expression of one of these genes, the epidermal growth factor receptor (EGFR), reverses the enhanced proliferation caused by telomerase. We conclude that telomerase may affect proliferation of epithelial cells not only by stabilizing telomeres, but also by affecting the expression of growth-promoting genes.


systematic_name: M19695
exact_source: Final annotated Gene list BX Tx vs AR up in AR
source_species_code: HS
GEO_id: GSE1563
contributor: Jean Junior
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in kidney biopsies from patients with acute transplant rejection compared to the biopsies from patients with well functioning kidneys more than 1-year post transplant.

description_full:
[cell repeats an earlier one in this file: 1518 characters]


description_brief: Genes induced in the liver during hepatitis B (HBV) viral clearance in chimpanzees.
systematic_name: M11620
exact_source: Table 3S
source_species_code: HS
contributor: Kate Stafford
contrib_organization: MSigDB Team
description_full:
  Previous studies in hepatitis B virus (HBV)-infected humans and chimpanzees suggest that control of HBV infection involves the cells, effector functions, and molecular mediators of the immune response. The objective of the current study was to identify, in the liver of acutely HBV-infected chimpanzees, the spectrum of virus-induced and immune response-related genes that regulate the infection. The results demonstrate that HBV does not induce any genes during entry and expansion, suggesting it is a stealth virus early in the infection. In contrast, a large number of T cell-derived IFN-gamma-regulated genes are induced in the liver during viral clearance, reflecting the impact of an adaptive T cell response that inhibits viral replication and kills infected cells, thereby terminating the infection.


description_brief: Genes down-regulated in MCF-7 cells (breast cancer) by estradiol (E2) [PubChem=5757].
systematic_name: M3002
exact_source: Tables 2-5: E2 down-regulated genes
source_species_code: HS
GEO_id: GSE848
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Selective estrogen receptor modulators (SERMs) such as tamoxifen are effective in the treatment of many estrogen receptor-positive breast cancers and have also proven to be effective in the prevention of breast cancer in women at high risk for the disease. The comparative abilities of tamoxifen versus raloxifene in breast cancer prevention are currently being compared in the Study of Tamoxifen and Raloxifene trial. To better understand the actions of these compounds in breast cancer, we have examined their effects on the expression of approximately 12,000 genes, using Affymetrix GeneChip microarrays, with quantitative PCR verification in many cases, categorizing their actions as agonist, antagonist, or partial agonist/antagonist. Analysis of gene stimulation and inhibition by the SERMs trans-hydroxytamoxifen (TOT) and raloxifene (Ral) or ICI 182,780 (ICI) and by estradiol (E2) in estrogen receptor-containing MCF-7 human breast cancer cells revealed that (a) TOT was the most E2-like of the three compounds, (b) all three compounds either partially or fully antagonized the action of E2 on most genes, with the order of antagonist activity being ICI > Ral > TOT, (c) TOT and Ral, but not ICI, displayed partial agonist/partial antagonist activity on a number of E2-regulated genes, (d) several stimulatory cell cycle-related genes were down-regulated exclusively by ICI, (e) the estrogen-like activity of Ral nearly always overlapped with that of TOT, indicating that Ral has little unique agonist activity different from that of TOT, and (f) some genes were specifically up-regulated by TOT but not Ral, ICI, or E2. Hence, gene expression profiling can discern fundamental differences among SERMs and provides insight into the distinct biologies of TOT, Ral, and ICI in breast cancer.


description_brief: Genes identified by ChIP within the high-affinity group of MYC [GeneID=4609] targets.
systematic_name: M3456
exact_source: Table 1
source_species_code: HS
contributor: Yujin Hoshida
contrib_organization: Broad Institute
description_full:
  The transcription factor Myc is induced by mitogenic signals and regulates downstream cellular responses. If overexpressed, Myc promotes malignant transformation. Myc modulates expression of diverse genes in experimental systems, but few are proven direct targets. Here, we present a large-scale screen for genomic Myc-binding sites in live human cells. We used bioinformatics to select consensus DNA elements (CACGTG or E-boxes) situated in the 5' regulatory region of genes and measured Myc binding to those sequences in vivo by quantitative chromatin immunoprecipitation. Strikingly, most promoter-associated E-boxes showed selective recovery with Myc, unlike non-E-box promoters or E-boxes in bulk genomic DNA. Promoter E-boxes were distributed in two groups bound by Myc at distinct frequencies. The high-affinity group included an estimated 11% of all cellular loci, was highly conserved among different cells, and was bound independently of Myc expression levels. Overexpressed Myc associated at increased frequency with low-affinity targets and, at extreme levels, also with other sequences, suggesting that some binding was not sequence-specific. The strongest DNA-sequence parameter defining high-affinity targets was the location of E-boxes within CpG islands, correlating with an open, preacetylated state of chromatin. Myc further enhanced histone acetylation, with or without accompanying induction of mRNA expression. Our findings point to a high regulatory and biological diversity among Myc-target genes.


description_brief: Genes up-regulated in mast cells (MC) after stimulation with a bacterial lipopolysaccharide (LPS).
systematic_name: M1911
exact_source: Table 3-IS
source_species_code: HS
contributor: Kate Stafford
contrib_organization: MSigDB Team
description_full:
  Rodent mast cells (MCs) are reported to play a pivotal role in both innate and adaptive immunity. However, there is so far no evidence that human MCs are involved in innate immunity. We found that a functional Toll-like receptor 4 (TLR4) was expressed on human MCs when it was up-regulated by interferon gamma (IFN-gamma). To systematically explore how human MCs modulate the immune system following TLR4-mediated activation and FcepsilonRI aggregation, we used high-density oligonucleotide probe arrays (GeneChip) to compare the lipopolysaccharide (LPS)-induced gene expression profile with the IgE/anti-IgE-mediated profile in MCs. Both a shared core response, and LPS- or anti-IgE-specific programs of gene expression were observed in MCs. Furthermore, MCs exhibited an antiviral response gene program in response to IFN-gamma, and LPS sustained that expression. Compared with the LPS-stimulated gene expression profile of human peripheral blood mononuclear cells, LPS-stimulated MCs specifically induced a subset of genes that included a Th2 cytokine and chemokines that recruit Th2 cells and eosinophils. These results reveal that human MCs express tailored pathogen- and antigen-specific immune responses and that human MCs may play important roles in innate and adaptive immunity.


systematic_name: M1475
exact_source: Final annotated Gene list BX Tx vs AR down in AR
source_species_code: HS
GEO_id: GSE1563
contributor: Jean Junior
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in kidney biopsies from patients with acute transplant rejection compared to the biopsies from patients with well functioning kidneys more than 1-year post transplant.

description_full:
[cell repeats an earlier one in this file: 1518 characters]


systematic_name: M4023
exact_source: Final annotated Gene list BX C vs Tx up in Tx
source_species_code: HS
GEO_id: GSE1563
contributor: Jean Junior
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in kidney biopsies from patients with well functioning kidneys more than 1-year post transplant compared to the biopsies from normal living kidney donors.

description_full:
[cell repeats an earlier one in this file: 1518 characters]


description_brief: The 'stemnes' signature: genes up-regulated and common to 6 human embryonic stem cell lines tested.
systematic_name: M4282
exact_source: Table 2S
source_species_code: HS
contributor: Kate Stafford
contrib_organization: MSigDB Team
description_full:
  Human embryonic stem (huES) cells have the ability to differentiate into a variety of cell lineages and potentially provide a source of differentiated cells for many therapeutic uses. However, little is known about the mechanism of differentiation of huES cells and factors regulating cell development. We have used high-quality microarrays containing 16 659 seventy-base pair oligonucleotides to examine gene expression in 6 of the 11 available huES cell lines. Expression was compared against pooled RNA from multiple tissues (universal RNA) and genes enriched in huES cells were identified. All 6 cell lines expressed multiple markers of the undifferentiated state and shared significant homology in gene expression (overall similarity coefficient > 0.85).A common subset of 92 genes was identified that included Nanog, GTCM-1, connexin 43 (GJA1), oct-4, and TDGF1 (cripto). Gene expression was confirmed by a variety of techniques including comparison with databases, reverse transcriptase-polymerase chain reaction, focused cDNA microarrays, and immunocytochemistry. Comparison with published stemness genes revealed a limited overlap, suggesting little similarity with other stem cell populations. Several novel ES cell-specific expressed sequence tags were identified and mapped to the human genome. These results represent the first detailed characterization of undifferentiated huES cells and provide a unique set of markers to profile and better understand the biology of huES cells.


description_brief: Top genes down-regulated at day 5 of Cre-Lox induced APC [GeneID=324] knockout in the intestine.
systematic_name: M1432
exact_source: Table 1cS
source_species_code: MM
contributor: Kevin Vogelsang
contrib_organization: MSigDB Team
description_full:
  Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of beta-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Apc-deficient cells maintain a crypt progenitor-like phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.


systematic_name: M6434
exact_source: Table 3S: positively associated
source_species_code: HS
contributor: Kevin Vogelsang
contrib_organization: MSigDB Team
description_brief:
  Top 100 genes positively associated with T-cell acute lymphoblastic leukemia MLL T-ALL) expressing MLL-ENL fusion [GeneID=4297;4298].

description_full:
  Rearrangements of the MLL locus, located on human chromosome 11q23, are frequent in both infant and therapy-related leukemias. Gene expression analysis of MLL-rearranged B-precursor acute lymphoblastic leukemias (MLL B-ALLs) has identified these cases as a unique subtype of leukemia, characterized by the expression of genes associated with both lymphoid and myeloid hematopoietic lineages. Here we show that MLL fusions also generate a distinct genetic subtype of T-lineage ALL (MLL T-ALL), in which leukemic cells are characterized by an early arrest in thymocyte differentiation, with suggestive evidence of commitment to the gammadelta lineage. Interestingly, multiple genes linked to cell proliferation (eg, PCNA, MYC, CDK2, and POLA) were down-regulated in MLL-fusion samples, relative to those transformed by other T-ALL oncogenes (P <.000 001, Fisher exact test). Overall, MLL T-ALL cases consistently demonstrated increased levels of expression of a subset of major HOX genes--HOXA9, HOXA10, and HOXC6--and the MEIS1 HOX coregulator (P <.008, one-sided Wilcoxon test), a pattern of gene expression that was reiterated in MLL B-ALLs. However, expression of myeloid lineage genes, previously reported in MLL B-ALLs, was not identified in T-lineage cases with this abnormality, suggesting that myeloid gene dysregulation is dispensable in leukemic transformation mediated by MLL fusion proteins. Our findings implicate dysregulation of HOX gene family members as a dominant mechanism of leukemic transformation induced by chimeric MLL oncogenes.


systematic_name: M863
exact_source: Suppl. Data Table
source_species_code: HS
GEO_id: GSE1318
contributor: Kevin Vogelsang
contrib_organization: MSigDB Team
description_brief:
  Myb-regulated genes in MCF7 (breast cancer) and lung epithelial cell lines overexpressing MYBL2, MYBL1 or MYB [GeneID=4605;4603;4602].

description_full:
  The A-Myb and c-Myb transcription factors share a highly conserved DNA-binding domain and activate the same promoters in reporter gene assays. However, the two proteins have distinct biological activities, and expressing them individually in human cells leads to the activation of distinct sets of endogenous genes, suggesting that each protein has a unique transcriptional specificity. Here, the structural and functional features of the Myb proteins were compared, using assays of endogenous gene expression to measure changes in specificity. When the Myb proteins were tested in different cell types, they activated unique and nearly nonoverlapping sets of genes in each cellular context. Deletion and domain swap experiments identified small, discreet positive and negative elements in A-Myb and c-Myb that were required for the regulation of specific genes, such as DHRS2, DSIPI, and mim-1. The results suggest that individual functional elements in the transcriptional activation domains are responsible for activating specific cellular genes in a context-specific manner. The results also have important implications for interpreting results from reporter gene assays, which fail to detect the differences in activity identified through endogenous gene assays, and fusion protein constructs that alter the transcriptional activation domains and the activities of the Myb proteins.


systematic_name: M3069
exact_source: Table 2
source_species_code: HS
contributor: Kevin Vogelsang
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated during in vitro maturation of CD14+ [GeneID=929] monocytes (day 0) into immature (day 7) and mature dendritic cells (day 14).

description_full:
  Dendritic cells (DCs) are antigen-presenting cells that play a major role in initiating primary immune responses. We have utilized two independent approaches, DNA microarrays and proteomics, to analyze the expression profile of human CD14(+) blood monocytes and their derived DCs. Analysis of gene expression changes at the RNA level using oligonucleotide microarrays complementary to 6300 human genes showed that approximately 40% of the genes were expressed in DCs. A total of 255 genes (4%) were found to be regulated during DC differentiation or maturation. Most of these genes were not previously associated with DCs and included genes encoding secreted proteins as well as genes involved in cell adhesion, signaling, and lipid metabolism. Protein analysis of the same cell populations was done using two-dimensional gel electrophoresis. A total of 900 distinct protein spots were included, and 4% of them exhibited quantitative changes during DC differentiation and maturation. Differentially expressed proteins were identified by mass spectrometry and found to represent proteins with Ca(2+) binding, fatty acid binding, or chaperone activities as well as proteins involved in cell motility. In addition, proteomic analysis provided an assessment of post-translational modifications. The chaperone protein, calreticulin, was found to undergo cleavage, yielding a novel form. The combined oligonucleotide microarray and proteomic approaches have uncovered novel genes associated with DC differentiation and maturation and has allowed analysis of post-translational modifications of specific proteins as part of these processes.


systematic_name: M939
exact_source: Table 3S
source_species_code: HS
contributor: Kevin Vogelsang
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in hematopoietic progenitor cells (HPC) of B lymphocyte lineage CD34+CD45RA+CD10+ [GeneID=947;5788;4311].

description_full:
  The early stages of human lymphopoiesis are poorly characterized. Here, we compared the lymphoid potential of a novel umbilical cord blood CD34(+)CD45RA(hi)CD7(+) hematopoietic progenitor cell (HPC) population with that of CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs, previously proposed as candidate common lymphoid progenitors. Limiting-dilution and clonal analysis, fetal thymic organ cultures, and culture onto Notch ligand Delta-like-1-expressing OP9 cells, showed that although CD34(+)CD45RA(hi)CD7(+) HPCs could generate cells of the 3 lymphoid lineages, their potential was skewed toward the T/natural killer (T/NK) lineages. In contrast, CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs predominantly exhibited a B-cell potential. Gene expression profiling with DNA microarrays confirmed that CD34(+)CD45RA(hi)CD7(+) HPCs selectively expressed T-lymphoid and NK lineage-committed genes while retaining expression of genes affiliated to the granulomonocytic lineage, whereas CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs displayed a typical pro-B-cell transcription profile and essentially lacked genes unrelated to the B lineage. In addition, both populations could be generated in vitro from CD34(+)CD45RA(int)CD7(-) and CD34(+)CD45RA(hi)Lin(-) HPCs with mixed lymphomyeloid potential, from which they emerged independently with different growth/differentiation factor requirements. These findings indicate that CD34(+)CD45RA(hi)CD7(+) and CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs correspond to multipotent early lymphoid progenitors polarized toward either the T/NK or B lineage, respectively.


description_brief: Genes up-regulated in Wilm's tumor samples compared to fetal kidney.
systematic_name: M12621
exact_source: Suppl. Data: set A
source_species_code: HS
contributor: Kevin Vogelsang
contrib_organization: MSigDB Team
description_full:
  Wilms' tumor (WT) has been considered a prototype for arrested cellular differentiation in cancer, but previous studies have relied on selected markers. We have now performed an unbiased survey of gene expression in WTs using oligonucleotide microarrays. Statistical criteria identified 357 genes as differentially expressed between WTs and fetal kidneys. This set contained 124 matches to genes on a microarray used by Stuart and colleagues (Stuart RO, Bush KT, Nigam SK: Changes in global gene expression patterns during development and maturation of the rat kidney. Proc Natl Acad Sci USA 2001, 98:5649-5654) to establish genes with stage-specific expression in the developing rat kidney. Mapping between the two data sets showed that WTs systematically overexpressed genes corresponding to the earliest stage of metanephric development, and underexpressed genes corresponding to later stages. Automated clustering identified a smaller group of 27 genes that were highly expressed in WTs compared to fetal kidney and heterologous tumor and normal tissues. This signature set was enriched in genes encoding transcription factors. Four of these, PAX2, EYA1, HBF2, and HOXA11, are essential for cell survival and proliferation in early metanephric development, whereas others, including SIX1, MOX1, and SALL2, are predicted to act at this stage. SIX1 and SALL2 proteins were expressed in the condensing mesenchyme in normal human fetal kidneys, but were absent (SIX1) or reduced (SALL2) in cells at other developmental stages. These data imply that the blastema in WTs has progressed to the committed stage in the mesenchymal-epithelial transition, where it is partially arrested in differentiation. The WT-signature set also contained the Wnt receptor FZD7, the tumor antigen PRAME, the imprinted gene NNAT and the metastasis-associated transcription factor E1AF.


systematic_name: M999
exact_source: Table 2S
source_species_code: HS
contributor: Kevin Vogelsang
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in hematopoietic progenitor cells (HPC) of T lymphocyte and NK (natural killer) lineage.

description_full:
  The early stages of human lymphopoiesis are poorly characterized. Here, we compared the lymphoid potential of a novel umbilical cord blood CD34(+)CD45RA(hi)CD7(+) hematopoietic progenitor cell (HPC) population with that of CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs, previously proposed as candidate common lymphoid progenitors. Limiting-dilution and clonal analysis, fetal thymic organ cultures, and culture onto Notch ligand Delta-like-1-expressing OP9 cells, showed that although CD34(+)CD45RA(hi)CD7(+) HPCs could generate cells of the 3 lymphoid lineages, their potential was skewed toward the T/natural killer (T/NK) lineages. In contrast, CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs predominantly exhibited a B-cell potential. Gene expression profiling with DNA microarrays confirmed that CD34(+)CD45RA(hi)CD7(+) HPCs selectively expressed T-lymphoid and NK lineage-committed genes while retaining expression of genes affiliated to the granulomonocytic lineage, whereas CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs displayed a typical pro-B-cell transcription profile and essentially lacked genes unrelated to the B lineage. In addition, both populations could be generated in vitro from CD34(+)CD45RA(int)CD7(-) and CD34(+)CD45RA(hi)Lin(-) HPCs with mixed lymphomyeloid potential, from which they emerged independently with different growth/differentiation factor requirements. These findings indicate that CD34(+)CD45RA(hi)CD7(+) and CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs correspond to multipotent early lymphoid progenitors polarized toward either the T/NK or B lineage, respectively.


systematic_name: M19541
exact_source: Table 12S
source_species_code: HS
GEO_id: GSM38627,GSM201145,GSM139891,GSM161538,GSM201143,GSM201144
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes commonly down-regulated in human alveolar rhabdomyosarcoma (ARMS) and its mouse model overexpressing PAX3-FOXO1 [GeneID=5077;2308] fusion.

description_full:
  Alveolar rhabdomyosarcomas (ARMS) are highly malignant soft-tissue sarcomas that arise in children, adolescents, and young adults. Although formation and expression of the PAX-FKHR fusion genes is thought to be the initiating event in this cancer, the role of PAX-FKHR in the neoplastic process remains largely unknown in a progenitor cell that is undefined. We hypothesize that PAX-FKHR determine the ARMS progenitor to the skeletal muscle lineage, which when coupled to the inactivation and/or activation of critical cell signaling pathways leads to the formation of ARMS. Because a number of studies have proposed that mesenchymal stem cells (MSC) are the progenitor for several of the sarcomas, we tested this hypothesis in MSCs. We show that PAX-FKHR induce skeletal myogenesis in MSCs by transactivating MyoD and myogenin. Despite exhibiting enhanced growth in vitro, the PAX-FKHR-expressing populations do not form colonies in soft agar or tumors in mice. Expression of dominant-negative p53, or the SV40 early region, elicits tumor formation in some of the PAX-FKHR-expressing populations. Additional activation of the Ras signaling pathway leads to highly malignant tumor formation for all of the populations. The PAX-FKHR-expressing tumors were shown to have histologic, immunohistochemical, and gene expression profiles similar to human ARMS. Our results show the critical role played by PAX-FKHR in determining the molecular, myogenic, and histologic phenotype of ARMS. More importantly, we identify MSCs as a progenitor that can give rise to ARMS.


description_brief: Genes up-regulated in patients at the incipient stage of Alzheimer's disease.
systematic_name: M6520
exact_source: Web Table 6: Upregulated
source_species_code: HS
GEO_id: GSE1297
contributor: John Newman
contrib_organization: University of Washington
description_full:
  The pathogenesis of incipient Alzheimer's disease (AD) has been resistant to analysis because of the complexity of AD and the overlap of its early-stage markers with normal aging. Gene microarrays provide new tools for addressing complexity because they allow overviews of the simultaneous activity of multiple cellular pathways. However, microarray data interpretation is often hindered by low statistical power, high false positives or false negatives, and by uncertain relevance to functional endpoints. Here, we analyzed hippocampal gene expression of nine control and 22 AD subjects of varying severity on 31 separate microarrays. We then tested the correlation of each gene's expression with MiniMental Status Examination (MMSE) and neurofibrillary tangle (NFT) scores across all 31 subjects regardless of diagnosis. These well powered tests revealed a major transcriptional response comprising thousands of genes significantly correlated with AD markers. Several hundred of these genes were also correlated with AD markers across only control and incipient AD subjects (MMSE > 20). Biological process categories associated with incipient AD-correlated genes were identified statistically (ease program) and revealed up-regulation of many transcription factor/signaling genes regulating proliferation and differentiation, including tumor suppressors, oligodendrocyte growth factors, and protein kinase A modulators. In addition, up-regulation of adhesion, apoptosis, lipid metabolism, and initial inflammation processes occurred, and down-regulation of protein folding/metabolism/transport and some energy metabolism and signaling pathways took place. These findings suggest a new model of AD pathogenesis in which a genomically orchestrated up-regulation of tumor suppressor-mediated differentiation and involution processes induces the spread of pathology along myelinated axons.


systematic_name: M14151
exact_source: Table 1S
source_species_code: HS
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes up-regulated in HEK293 cells (embryonic kidney) at 6 h, 12 h or 24 h after infection with reovirus strain T3A (known as a strong inducer of apoptosis).

description_full:
  Reoviruses are a leading model for understanding cellular mechanisms of virus-induced apoptosis. Reoviruses induce apoptosis in multiple cell lines in vitro, and apoptosis plays a key role in virus-induced tissue injury of the heart and brain in vivo. The activation of transcription factors NF-kappaB and c-Jun are key events in reovirus-induced apoptosis, indicating that new gene expression is critical to this process. We used high-density oligonucleotide microarrays to analyze cellular transcriptional alterations in HEK293 cells after infection with reovirus strain T3A (i.e., apoptosis inducing) compared to infection with reovirus strain T1L (i.e., minimally apoptosis inducing) and uninfected cells. These strains also differ dramatically in their potential to induce apoptotic injury in hearts of infected mice in vivo-T3A is myocarditic, whereas T1L is not. Using high-throughput microarray analysis of over 12,000 genes, we identified differential expression of a defined subset of genes involved in apoptosis and DNA repair after reovirus infection. This provides the first comparative analysis of altered gene expression after infection with viruses of differing apoptotic phenotypes and provides insight into pathogenic mechanisms of virus-induced disease.


systematic_name: M15468
exact_source: Table 2S: Cluster d4
source_species_code: HS
GEO_id: GSE713
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Cluster d4: genes progressively down-regulated in WS1 cells (fibroblast) through 12 h after irradiation with high dose UV-C.

description_full:
[cell repeats an earlier one in this file: 1467 characters]


systematic_name: M4780
exact_source: Table 2S, 4S
source_species_code: HS
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes down-regulated in BT549 cells (breast cancer) by expression of SMARCE1 [GeneID=6605] off a retroviral vector.

description_full:
  Mutation of BRG1, hBRM, and their associated factors, INI1 and BAF57, in primary human tumors has suggested that inactivation of human SWI/SNF (hSWI/SNF) complexes may be involved in neoplastic transformation. BT549 is an invasive human breast carcinoma cell line that lacks expression of BAF57, a key hSWI/SNF subunit that mediates interaction with transcriptional activators and corepressors. In this study we investigated the role of BAF57 in suppressing tumorigenesis by establishing BT549 stable cell lines that expresses full-length BAF57 protein. BT549 clones expressing BAF57 demonstrated marked phenotypic changes, slow growth kinetics, and restoration of contact inhibition. Altered growth was found to be due in part to cell cycle arrest and induction of apoptosis. Furthermore, microarray analysis revealed that BAF57-mediated cell death was associated with up-regulation of proapoptotic genes including the tumor suppressor familial cylindromatosis (CYLD), which was found to be a direct target of BAF57 as determined by chromatin immunoprecipitation analysis. Increased expression of CYLD in BT549 cells induced apoptosis, while its suppression by small interfering RNA inhibited cell death in BAF57 expressing BT549 cells. These findings demonstrate the importance of BAF57 in cell growth regulation and provide a novel link between hSWI/SNF chromatin remodelers and apoptosis.


systematic_name: M9702
exact_source: Table 1
source_species_code: HS
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  50 most interesting genes up-regulated in the pancreatic cancer cell lines (AsPC1, Hs766T, MiaPaCa2, Panc1) but not in the non-neoplastic cells (HPDE) by decitabine (5-aza-2'-deoxycytidine) [PubChem=451668].

description_full:
  To identify potential targets for aberrant methylation in pancreatic cancer, we analyzed global changes in gene expression profiles of four pancreatic cancer cell lines after treatment with the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) and/or the histone deacetylase inhibitor trichostatin A. A substantial number of genes were induced 5-fold or greater by 5Aza-dC alone (631 transcripts), trichostatin A alone (1196 transcripts), and by treatment with both agents (857 transcripts). Four hundred and seventy-five genes were markedly (>5-fold) induced after 5Aza-dC treatment in pancreatic cancer cell lines but not in a nonneoplastic pancreatic epithelial cell line. The methylation status of 11 of these 475 genes was examined in a panel of 42 pancreatic cancers, and all 11 of these genes were aberrantly methylated in pancreatic cancer but rarely, if any, methylated in 10 normal pancreatic ductal epithelia. These genes include UCHL1 (methylated in 100% of 42 pancreatic cancers), NPTX2 (98%), SARP2 (95%), CLDN5 (93%), reprimo (86%), LHX1 (76%), WNT7A (71%), FOXE1 (69%), TJP2 (64%), CDH3 (19%), and ST14 (10%). Three of these 11 genes (NPTX2, SARP2, and CLDN5) were selected for further analysis in a larger panel of specimens, and aberrant methylation of at least one of these three genes was detectable in 100% of 43 primary pancreatic cancers and in 18 of 24 (75%) pancreatic juice samples obtained from patients with pancreatic cancer. Thus, a substantial number of genes are induced by 5Aza-dC treatment of pancreatic cancer cells, and many of them may represent novel targets for aberrant methylation in pancreatic carcinoma.


systematic_name: M97
exact_source: www-onderzoek.lumc.nl/ pathology/kidney/diabeticnephropathy/
source_species_code: HS
GEO_id: GSE1009
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes up-regulated in glomeruli of kidneys from patients with diabetic nephropathy (type 2 diabetes mellitus).

description_full:
  BACKGROUND: Diabetic nephropathy (DN) is a frequent complication in patients with diabetes mellitus. To find improved intervention strategies in this disease, it is necessary to investigate the molecular mechanisms involved. To obtain more insight into processes that lead to DN, messenger RNA expression profiles of diabetic glomeruli and glomeruli from healthy individuals were compared. METHODS: Two morphologically normal kidneys and 2 kidneys from patients with DN were used for the study. Glomerular RNA was hybridized in duplicate on Human Genome U95Av2 Arrays (Affymetrix, Santa Clara, CA). Several transcripts were tested further in independent patient groups and at the protein level by immunohistochemistry. RESULTS: Ninety-six genes were upregulated in diabetic glomeruli, whereas 519 genes were downregulated. The list of overexpressed genes in DN includes aquaporin 1, calpain 3, hyaluronoglucosidase, and platelet/endothelial cell adhesion molecule. The list of downregulated genes includes bone morphogenetic protein 2, vascular endothelial growth factor (VEGF), fibroblast growth factor 1, insulin-like growth factor binding protein 2, and nephrin. A decrease in VEGF and nephrin could be validated at the protein level and also at the RNA level in renal biopsy specimens from 5 additional patients with diabetes. CONCLUSION: Results of oligonucleotide microarray analyses on control and diabetic glomeruli are presented and discussed in their relation to vascular damage, mesangial matrix expansion, proliferation, and proteinuria. Our findings suggest that progression of DN might result from diminished tissue repair capability.


systematic_name: M14385
exact_source: Table 1S: fold change < 0
source_species_code: HS
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes down-regulated in fibroblasts with defective XPC [GeneID=7508] in response to cisplatin [PubChem=2767].

description_full:
  XPC is an important DNA damage recognition protein involved in DNA nucleotide excision repair. We have studied the role of the XPC protein in cisplatin treatment-mediated cell cycle regulation. Through the comparison of microarray data obtained from human normal fibroblasts and two individual XPC-defective cell lines, 486 genes were identified as XPC-responsive genes in the cisplatin treatment (with a minimal 1.5-fold change) and 297 of these genes were further mapped to biological pathways and gene ontologies. The cell cycle and cell proliferation-related genes were the most affected genes by the XPC defect in the cisplatin treatment. Many other cellular function genes were also affected by the XPC defect in the treatment. Western blot hybridization results revealed that the XPC defect reduced the p53 responses to the cisplatin treatment. The ability to activate caspase-3 was also attenuated in the XPC cells with the treatment. These results suggest that the XPC protein plays a critical role in initiating the cisplatin DNA damaging treatment-mediated signal transduction process, resulting in activation of the p53 pathway and cell cycle arrest that allow DNA repair and apoptosis to take place. These results reveal an important role of the XPC protein in the cancer prevention.


systematic_name: M5542
exact_source: http://pathology2.jhu.edu/pancreas/combi.pdf
source_species_code: HS
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  50 genes up-regulated in the pancreatic cancer cell lines (AsPC1, Hs766T, MiaPaCa2, Panc1) but not in the non-neoplastic cells (HPDE) by the combination of decitabine  and TSA [PubChem=451668;5562].

description_full:
  To identify potential targets for aberrant methylation in pancreatic cancer, we analyzed global changes in gene expression profiles of four pancreatic cancer cell lines after treatment with the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) and/or the histone deacetylase inhibitor trichostatin A. A substantial number of genes were induced 5-fold or greater by 5Aza-dC alone (631 transcripts), trichostatin A alone (1196 transcripts), and by treatment with both agents (857 transcripts). Four hundred and seventy-five genes were markedly (>5-fold) induced after 5Aza-dC treatment in pancreatic cancer cell lines but not in a nonneoplastic pancreatic epithelial cell line. The methylation status of 11 of these 475 genes was examined in a panel of 42 pancreatic cancers, and all 11 of these genes were aberrantly methylated in pancreatic cancer but rarely, if any, methylated in 10 normal pancreatic ductal epithelia. These genes include UCHL1 (methylated in 100% of 42 pancreatic cancers), NPTX2 (98%), SARP2 (95%), CLDN5 (93%), reprimo (86%), LHX1 (76%), WNT7A (71%), FOXE1 (69%), TJP2 (64%), CDH3 (19%), and ST14 (10%). Three of these 11 genes (NPTX2, SARP2, and CLDN5) were selected for further analysis in a larger panel of specimens, and aberrant methylation of at least one of these three genes was detectable in 100% of 43 primary pancreatic cancers and in 18 of 24 (75%) pancreatic juice samples obtained from patients with pancreatic cancer. Thus, a substantial number of genes are induced by 5Aza-dC treatment of pancreatic cancer cells, and many of them may represent novel targets for aberrant methylation in pancreatic carcinoma.


description_brief: Genes down-regulated in pulpal tissue extracted from carious teeth.
systematic_name: M1278
exact_source: Table 3S
source_species_code: HS
GEO_id: GSE1629
contributor: John Newman
contrib_organization: University of Washington
description_full:
  High-throughput characterisation of the molecular response of pulpal tissue under carious lesions may contribute to improved future diagnosis and treatment. To identify genes associated with this process, oligonucleotide microarrays containing approximately 15,000 human sequences were screened using pooled total RNA isolated from pulpal tissue from both healthy and carious teeth. Data analysis identified 445 genes with 2-fold or greater difference in expression level, with 85 more abundant in health and 360 more abundant in disease. Subsequent gene ontological grouping identified a variety of processes and functions potentially activated or down-modulated during caries. Validation of microarray results was obtained by a combination of real-time and semi-quantitative PCR for selected genes, confirming down-regulation of Dentin Matrix Protein-1 (DMP-1), SLIT 2, Period-2 (PER 2), Period-3 (PER 3), osteoadherin, Glypican-3, Midkine, activin receptor interacting protein-1 (AIP 1), osteoadherin and growth hormone receptor (GHR), and up-regulation of Adrenomedullin (ADM), Interleukin-11 (IL-11), Bone sialoprotein (BSP), matrix Gla protein (MGP), endothelial cell growth factor-1 (ECGF 1), inhibin beta A and orosomucoid-1 (ORM 1), in diseased pulp. Real-time PCR analyses of ADM and DMP-1 in a panel of healthy and carious pulpal tissue and also in immune system cells highlighted the heterogeneity of caries and indicated increased expression of ADM in neutrophils activated by bacterial products. In contrast, DMP-1 was predominantly expressed by cells native to healthy pulpal tissue. This study has greatly extended our molecular knowledge of dental tissue disease and identified involvement of genes previously unassociated with this process.


systematic_name: M9893
exact_source: Table 5S: Fold change > 1
source_species_code: HS
GEO_id: GSE362
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes whose expression increases with age in normal kidney, excluding those with higher expression in blood.

description_full:
  In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age.


systematic_name: M3063
exact_source: Table 1S
source_species_code: HS
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes down-regulated in HEK293 cells (embryonic kidney) at 6 h, 12 h or 24 h after infection with reovirus strain T3A (known as a strong inducer of apoptosis).

description_full:
  Reoviruses are a leading model for understanding cellular mechanisms of virus-induced apoptosis. Reoviruses induce apoptosis in multiple cell lines in vitro, and apoptosis plays a key role in virus-induced tissue injury of the heart and brain in vivo. The activation of transcription factors NF-kappaB and c-Jun are key events in reovirus-induced apoptosis, indicating that new gene expression is critical to this process. We used high-density oligonucleotide microarrays to analyze cellular transcriptional alterations in HEK293 cells after infection with reovirus strain T3A (i.e., apoptosis inducing) compared to infection with reovirus strain T1L (i.e., minimally apoptosis inducing) and uninfected cells. These strains also differ dramatically in their potential to induce apoptotic injury in hearts of infected mice in vivo-T3A is myocarditic, whereas T1L is not. Using high-throughput microarray analysis of over 12,000 genes, we identified differential expression of a defined subset of genes involved in apoptosis and DNA repair after reovirus infection. This provides the first comparative analysis of altered gene expression after infection with viruses of differing apoptotic phenotypes and provides insight into pathogenic mechanisms of virus-induced disease.


systematic_name: M4665
exact_source: www-onderzoek.lumc.nl/ pathology/kidney/diabeticnephropathy/
source_species_code: HS
GEO_id: GSE1009
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes down-regulated in glomeruli of kidneys from patients with diabetic nephropathy (type 2 diabetes mellitus).

description_full:
  BACKGROUND: Diabetic nephropathy (DN) is a frequent complication in patients with diabetes mellitus. To find improved intervention strategies in this disease, it is necessary to investigate the molecular mechanisms involved. To obtain more insight into processes that lead to DN, messenger RNA expression profiles of diabetic glomeruli and glomeruli from healthy individuals were compared. METHODS: Two morphologically normal kidneys and 2 kidneys from patients with DN were used for the study. Glomerular RNA was hybridized in duplicate on Human Genome U95Av2 Arrays (Affymetrix, Santa Clara, CA). Several transcripts were tested further in independent patient groups and at the protein level by immunohistochemistry. RESULTS: Ninety-six genes were upregulated in diabetic glomeruli, whereas 519 genes were downregulated. The list of overexpressed genes in DN includes aquaporin 1, calpain 3, hyaluronoglucosidase, and platelet/endothelial cell adhesion molecule. The list of downregulated genes includes bone morphogenetic protein 2, vascular endothelial growth factor (VEGF), fibroblast growth factor 1, insulin-like growth factor binding protein 2, and nephrin. A decrease in VEGF and nephrin could be validated at the protein level and also at the RNA level in renal biopsy specimens from 5 additional patients with diabetes. CONCLUSION: Results of oligonucleotide microarray analyses on control and diabetic glomeruli are presented and discussed in their relation to vascular damage, mesangial matrix expansion, proliferation, and proteinuria. Our findings suggest that progression of DN might result from diminished tissue repair capability.


systematic_name: M11213
exact_source: http://pathology2.jhu.edu/pancreas/TSA.pdf
source_species_code: HS
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  50 most interesting genes up-regulated in pancreatic cancer cell lines (AsPC1, Hs766T, MiaPaCa2, Panc1) but not in the non-neoplastic cells (HPDE) by TSA [PubChem=5562].

description_full:
  To identify potential targets for aberrant methylation in pancreatic cancer, we analyzed global changes in gene expression profiles of four pancreatic cancer cell lines after treatment with the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) and/or the histone deacetylase inhibitor trichostatin A. A substantial number of genes were induced 5-fold or greater by 5Aza-dC alone (631 transcripts), trichostatin A alone (1196 transcripts), and by treatment with both agents (857 transcripts). Four hundred and seventy-five genes were markedly (>5-fold) induced after 5Aza-dC treatment in pancreatic cancer cell lines but not in a nonneoplastic pancreatic epithelial cell line. The methylation status of 11 of these 475 genes was examined in a panel of 42 pancreatic cancers, and all 11 of these genes were aberrantly methylated in pancreatic cancer but rarely, if any, methylated in 10 normal pancreatic ductal epithelia. These genes include UCHL1 (methylated in 100% of 42 pancreatic cancers), NPTX2 (98%), SARP2 (95%), CLDN5 (93%), reprimo (86%), LHX1 (76%), WNT7A (71%), FOXE1 (69%), TJP2 (64%), CDH3 (19%), and ST14 (10%). Three of these 11 genes (NPTX2, SARP2, and CLDN5) were selected for further analysis in a larger panel of specimens, and aberrant methylation of at least one of these three genes was detectable in 100% of 43 primary pancreatic cancers and in 18 of 24 (75%) pancreatic juice samples obtained from patients with pancreatic cancer. Thus, a substantial number of genes are induced by 5Aza-dC treatment of pancreatic cancer cells, and many of them may represent novel targets for aberrant methylation in pancreatic carcinoma.


systematic_name: M1810
exact_source: Table 2S: Cluster#=6
source_species_code: HS
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Cluster G6: genes increasingly down-regulated in NHEK cells (normal keratinocyte) after UV-B irradiation.

description_full:
[cell repeats an earlier one in this file: 2087 characters]


systematic_name: M4308
exact_source: http://pathology2.jhu.edu/pancreas/475genes5aza_dc.htm
source_species_code: HS
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes up-regulated in the pancreatic cancer cell lines (AsPC1, Hs766T, MiaPaCa2, Panc1) but not in the non-neoplastic cells (HPDE) by decitabine (5-aza-2'-deoxycytidine) [PubChem=451668].

description_full:
[cell repeats an earlier one in this file: 1649 characters]


systematic_name: M1804
exact_source: Table 1S, 3S
source_species_code: HS
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes up-regulated in BT549 cells (breast cancer) by expression of SMARCE1 [GeneID=6605] off a retroviral vector.

description_full:
  Mutation of BRG1, hBRM, and their associated factors, INI1 and BAF57, in primary human tumors has suggested that inactivation of human SWI/SNF (hSWI/SNF) complexes may be involved in neoplastic transformation. BT549 is an invasive human breast carcinoma cell line that lacks expression of BAF57, a key hSWI/SNF subunit that mediates interaction with transcriptional activators and corepressors. In this study we investigated the role of BAF57 in suppressing tumorigenesis by establishing BT549 stable cell lines that expresses full-length BAF57 protein. BT549 clones expressing BAF57 demonstrated marked phenotypic changes, slow growth kinetics, and restoration of contact inhibition. Altered growth was found to be due in part to cell cycle arrest and induction of apoptosis. Furthermore, microarray analysis revealed that BAF57-mediated cell death was associated with up-regulation of proapoptotic genes including the tumor suppressor familial cylindromatosis (CYLD), which was found to be a direct target of BAF57 as determined by chromatin immunoprecipitation analysis. Increased expression of CYLD in BT549 cells induced apoptosis, while its suppression by small interfering RNA inhibited cell death in BAF57 expressing BT549 cells. These findings demonstrate the importance of BAF57 in cell growth regulation and provide a novel link between hSWI/SNF chromatin remodelers and apoptosis.


systematic_name: M11338
exact_source: Table 2S: Cluster d3
source_species_code: HS
GEO_id: GSE713
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Cluster d3: genes progressively down-regulated in WS1 cells (fibroblast) through 12 h irradiation with high dose UV-C.

description_full:
[cell repeats an earlier one in this file: 1467 characters]


description_brief: Genes down-regulated in at least 8 of 11 sarcoma cell lines by trabectedin [PubChem=3199].
systematic_name: M15123
exact_source: Suppl.data on the web
source_species_code: HS
contributor: John Newman
contrib_organization: University of Washington
description_full:
  Ecteinascidin 743 (ET-743; Yondelis, Trabectedin) is a marine anticancer agent that induces long-lasting objective remissions and tumor control in a subset of patients with pretreated/resistant soft-tissue sarcoma. Drug-induced tumor control is achievable in 22% of such patients, but there is no clear indication of the molecular features correlated with clinical sensitivity/resistance to ET-743. Nine low-passage, soft-tissue sarcoma cell lines, explanted from chemo-naive patients with different patterns of sensitivity, have been profiled with a cDNA microarray containing 6,700 cancer-related genes. The molecular signature of these cell lines was analyzed at baseline and at four different times after ET-743 exposure. The association of levels of TP53 mutation and TP73 expression with ET-743 sensitivity and cell cycle kinetics after treatment was also analyzed. Gene expression profile analysis revealed up-regulation of 86 genes and down-regulation of 244 genes in response to ET-743. The ET-743 gene expression signature identified a group of genes related with cell cycle control, stress, and DNA-damage response (JUNB, ATF3, CS-1, SAT, GADD45B, and ID2) that were up-regulated in all the cell lines studied. The transcriptional signature 72 hours after ET-743 administration, associated with ET-743 sensitivity, showed a more efficient induction of genes involved in DNA-damage response and apoptosis, such as RAD17, BRCA1, PAR4, CDKN1A, and P53DINP1, in the sensitive cell line group. The transcriptional signature described here may lead to the identification of ET-743 downstream mediators and transcription regulators and the proposal of strategies by which ET-743-sensitive tumors may be identified.


systematic_name: M15103
exact_source: Table 1AS: Direction = Up
source_species_code: HS
GEO_id: GSE12064
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in A4573 cells (Ewing's sarcoma, ESFT) after knockdown of BMI1 [GeneID=648] by RNAi.

description_full:
  Deregulation of the polycomb group gene BMI-1 is implicated in the pathogenesis of many human cancers. In this study, we have investigated if the Ewing sarcoma family of tumors (ESFT) expresses BMI-1 and whether it functions as an oncogene in this highly aggressive group of bone and soft tissue tumors. Our data show that BMI-1 is highly expressed by ESFT cells and that, although it does not significantly affect proliferation or survival, BMI-1 actively promotes anchorage-independent growth in vitro and tumorigenicity in vivo. Moreover, we find that BMI-1 promotes the tumorigenicity of both p16 wild-type and p16-null cell lines, demonstrating that the mechanism of BMI-1 oncogenic function in ESFT is, at least in part, independent of CDKN2A repression. Expression profiling studies of ESFT cells following BMI-1 knockdown reveal that BMI-1 regulates the expression of hundreds of downstream target genes including, in particular, genes involved in both differentiation and development as well as cell-cell and cell-matrix adhesion. Gain and loss of function assays confirm that BMI-1 represses the expression of the adhesion-associated basement membrane protein nidogen 1. In addition, although BMI-1 promotes ESFT adhesion, nidogen 1 inhibits cellular adhesion in vitro. Together, these data support a pivotal role for BMI-1 ESFT pathogenesis and suggest that its oncogenic function in these tumors is in part mediated through modulation of adhesion pathways.


systematic_name: M8144
exact_source: Table 4S: 6hr
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in HL-60 cells (acute promyelocytic leukemia, APL) after treatment with the aminopeptidase inhibitor tosedostat (CHR-2797) [PubChem=15547703] for 6 h.

description_full:
  CHR-2797 is a novel metalloenzyme inhibitor that is converted into a pharmacologically active acid product (CHR-79888) inside cells. CHR-79888 is a potent inhibitor of a number of intracellular aminopeptidases, including leucine aminopeptidase. CHR-2797 exerts antiproliferative effects against a range of tumor cell lines in vitro and in vivo and shows selectivity for transformed over nontransformed cells. Its antiproliferative effects are at least 300 times more potent than the prototypical aminopeptidase inhibitor, bestatin. However, the mechanism by which inhibition of these enzymes leads to proliferative changes is not understood. Gene expression microarrays were used to profile changes in mRNA expression levels in the human promyelocytic leukemia cell line HL-60 treated with CHR-2797. This analysis showed that CHR-2797 treatment induced a transcriptional response indicative of amino acid depletion, the amino acid deprivation response, which involves up-regulation of amino acid synthetic genes, transporters, and tRNA synthetases. These changes were confirmed in other leukemic cell lines sensitive to the antiproliferative effects of CHR-2797. Furthermore, CHR-2797 treatment inhibited phosphorylation of mTOR substrates and reduced protein synthesis in HL-60 cells, both also indicative of amino acid depletion. Treatment with CHR-2797 led to an increase in the concentration of intracellular small peptides, the substrates of aminopeptidases. It is suggested that aminopeptidase inhibitors, such as CHR-2797 and bestatin, deplete sensitive tumor cells of amino acids by blocking protein recycling, and this generates an antiproliferative effect. CHR-2797 is orally bioavailable and currently undergoing phase II clinical investigation in the treatment of myeloid leukemia.


systematic_name: M19907
exact_source: Table 4S: 6hr
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in HL-60 cells (acute promyelocytic leukemia, APL) after treatment with the aminopeptidase inhibitor tosedostat (CHR-2797) [PubChem=15547703] for 6 h.

description_full:
  CHR-2797 is a novel metalloenzyme inhibitor that is converted into a pharmacologically active acid product (CHR-79888) inside cells. CHR-79888 is a potent inhibitor of a number of intracellular aminopeptidases, including leucine aminopeptidase. CHR-2797 exerts antiproliferative effects against a range of tumor cell lines in vitro and in vivo and shows selectivity for transformed over nontransformed cells. Its antiproliferative effects are at least 300 times more potent than the prototypical aminopeptidase inhibitor, bestatin. However, the mechanism by which inhibition of these enzymes leads to proliferative changes is not understood. Gene expression microarrays were used to profile changes in mRNA expression levels in the human promyelocytic leukemia cell line HL-60 treated with CHR-2797. This analysis showed that CHR-2797 treatment induced a transcriptional response indicative of amino acid depletion, the amino acid deprivation response, which involves up-regulation of amino acid synthetic genes, transporters, and tRNA synthetases. These changes were confirmed in other leukemic cell lines sensitive to the antiproliferative effects of CHR-2797. Furthermore, CHR-2797 treatment inhibited phosphorylation of mTOR substrates and reduced protein synthesis in HL-60 cells, both also indicative of amino acid depletion. Treatment with CHR-2797 led to an increase in the concentration of intracellular small peptides, the substrates of aminopeptidases. It is suggested that aminopeptidase inhibitors, such as CHR-2797 and bestatin, deplete sensitive tumor cells of amino acids by blocking protein recycling, and this generates an antiproliferative effect. CHR-2797 is orally bioavailable and currently undergoing phase II clinical investigation in the treatment of myeloid leukemia.


systematic_name: M17915
exact_source: Table 4S: 24 h
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in HL-60 cells (acute promyelocytic leukemia, APL) after treatment with the aminopeptidase inhibitor tosedostat (CHR-2797) [PubChem=15547703] for 24 h.

description_full:
[cell repeats an earlier one in this file: 1793 characters]


systematic_name: M8525
exact_source: Table 4S: 24 h
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in HL-60 cells (acute promyelocytic leukemia, APL) after treatment with the aminopeptidase inhibitor tosedostat (CHR-2797) [PubChem=15547703] for 24 h.

description_full:
[cell repeats an earlier one in this file: 1793 characters]


systematic_name: M4210
exact_source: Suppl. Data File 1: HER2-18_Group3
source_species_code: HS
GEO_id: GSE8139,GSE8141,GSE8140
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  The 'group 3 set' of genes associated with acquired endocrine therapy resistance in breast tumors expressing ESR1 and ERBB2 [GeneID=2099;2064].

description_full:
  The effectiveness of therapies targeting specific pathways in breast cancer, such as the estrogen receptor or HER2, is limited because many tumors manifest resistance, either de novo or acquired, during the course of treatment. To investigate molecular mechanisms of resistance, we used two xenograft models of estrogen receptor-positive (ER+) breast cancer, one with and one without HER2 overexpression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (G). Another group received ED plus the antiestrogen fulvestrant (MCF7 wt only). Tumors with acquired or de novo resistance to these endocrine therapies were profiled for gene expression and compared with tumors in the E2 control group. One class of genes underexpressed in endocrine-resistant tumors (relative to E2-treated tumors) were estrogen inducible in vitro and associated with ER+ human breast cancers (luminal subtype). Another class of genes overexpressed in tumors with acquired resistance in both models represented transcriptional targets of HER2 signaling and was associated with ER-/HER2+ human cancers (ERBB2+ subtype). A third class of genes overexpressed in MCF7/HER2-18 tumors exhibiting de novo resistance to tamoxifen was associated with ER+ human cancers but not with estrogen-regulated genes. Thus, in response to various endocrine therapy regimens, these xenograft breast tumors shut down classic estrogen signaling and activate alternative pathways such as HER2 that contribute to treatment resistance. Over time, the molecular phenotype of breast cancer can change.


systematic_name: M13661
exact_source: Suppl. Data File 1: WT_Group5
source_species_code: HS
GEO_id: GSE8140,GSE8139,GSE8141
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  The 'group 5 set' of genes associated with acquired endocrine therapy resistance in breast tumors expressing ESR1 but not ERBB2 [GeneID=2099;2064].

description_full:
  The effectiveness of therapies targeting specific pathways in breast cancer, such as the estrogen receptor or HER2, is limited because many tumors manifest resistance, either de novo or acquired, during the course of treatment. To investigate molecular mechanisms of resistance, we used two xenograft models of estrogen receptor-positive (ER+) breast cancer, one with and one without HER2 overexpression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (G). Another group received ED plus the antiestrogen fulvestrant (MCF7 wt only). Tumors with acquired or de novo resistance to these endocrine therapies were profiled for gene expression and compared with tumors in the E2 control group. One class of genes underexpressed in endocrine-resistant tumors (relative to E2-treated tumors) were estrogen inducible in vitro and associated with ER+ human breast cancers (luminal subtype). Another class of genes overexpressed in tumors with acquired resistance in both models represented transcriptional targets of HER2 signaling and was associated with ER-/HER2+ human cancers (ERBB2+ subtype). A third class of genes overexpressed in MCF7/HER2-18 tumors exhibiting de novo resistance to tamoxifen was associated with ER+ human cancers but not with estrogen-regulated genes. Thus, in response to various endocrine therapy regimens, these xenograft breast tumors shut down classic estrogen signaling and activate alternative pathways such as HER2 that contribute to treatment resistance. Over time, the molecular phenotype of breast cancer can change.


systematic_name: M8776
exact_source: Table 1S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in at least one of three multiple myeloma (MM) cell lines treated with the DNA hypomethylating agent decitabine (5-aza-2'-deoxycytidine) [PubChem=451668].

description_full:
  To identify epigenetically silenced cancer-related genes and to determine molecular effects of 5-aza-2'-deoxycytidine (Aza-dC) and/or trichostatin A (TSA) in multiple myeloma (MM), we analyzed global changes in gene expression profiles of three MM cell lines by microarray analysis. We identified up-regulation of several genes whose epigenetic silencing in MM is well known. However, much more importantly, we identified a large number of epigenetically inactivated cancer-related genes that are involved in various physiologic processes and whose epigenetic regulation in MM was unknown thus far. In addition, drug treatment of MM cell lines resulted in down-regulation of several MM proliferation-associated factors (i.e., MAF, CCND1/2, MYC, FGFR3, MMSET). Ten Aza-dC and/or TSA up-regulated genes (CPEB1, CD9, GJA1, BCL7c, GADD45G, AKAP12, TFPI2, CCNA1, SPARC, and BNIP3) were selected for methylation analysis in six MM cell lines, 24 samples from patients with monoclonal gammopathy of undetermined significance (MGUS), and 111 samples from patients with MM. Methylation frequencies of these genes ranged between 0% and 17% in MGUS samples and between 5% and 50% in MM samples. Interestingly, methylation of SPARC and BNIP3 was statistically significantly associated with a poor overall survival of MM patients (P = 0.003 and P = 0.017, respectively). Moreover, SPARC methylation was associated with loss of SPARC protein expression by immunostaining in a subset of MM patients. In conclusion, we identified new targets for aberrant methylation in monoclonal gammopathies, and our results suggest that DNA methyltransferase and histone deacetylase inhibition might play an important role in the future treatment of patients with MM.


systematic_name: M3185
exact_source: Table 4S: Aza-dC down-regulated
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in at least one of three multiple myeloma (MM) cell lines treated with the DNA hypomethylating agent decitabine (5-aza-2'-deoxycytidine) [PubChem=451668].

description_full:
  To identify epigenetically silenced cancer-related genes and to determine molecular effects of 5-aza-2'-deoxycytidine (Aza-dC) and/or trichostatin A (TSA) in multiple myeloma (MM), we analyzed global changes in gene expression profiles of three MM cell lines by microarray analysis. We identified up-regulation of several genes whose epigenetic silencing in MM is well known. However, much more importantly, we identified a large number of epigenetically inactivated cancer-related genes that are involved in various physiologic processes and whose epigenetic regulation in MM was unknown thus far. In addition, drug treatment of MM cell lines resulted in down-regulation of several MM proliferation-associated factors (i.e., MAF, CCND1/2, MYC, FGFR3, MMSET). Ten Aza-dC and/or TSA up-regulated genes (CPEB1, CD9, GJA1, BCL7c, GADD45G, AKAP12, TFPI2, CCNA1, SPARC, and BNIP3) were selected for methylation analysis in six MM cell lines, 24 samples from patients with monoclonal gammopathy of undetermined significance (MGUS), and 111 samples from patients with MM. Methylation frequencies of these genes ranged between 0% and 17% in MGUS samples and between 5% and 50% in MM samples. Interestingly, methylation of SPARC and BNIP3 was statistically significantly associated with a poor overall survival of MM patients (P = 0.003 and P = 0.017, respectively). Moreover, SPARC methylation was associated with loss of SPARC protein expression by immunostaining in a subset of MM patients. In conclusion, we identified new targets for aberrant methylation in monoclonal gammopathies, and our results suggest that DNA methyltransferase and histone deacetylase inhibition might play an important role in the future treatment of patients with MM.


systematic_name: M6890
exact_source: Table 4S: TSA down-regulated
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in at least one of three multiple myeloma (MM) cell lines by TSA [PubChem=5562].

description_full:
[cell repeats an earlier one in this file: 1738 characters]


systematic_name: M14127
exact_source: Table 3S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in multiple myeloma (MM) cell lines treated with both decitabine [PubChem=451668] TSA [PubChem=5562].

description_full:
[cell repeats an earlier one in this file: 1738 characters]


systematic_name: M7623
exact_source: Table 4S: Aza-dC/TSA down-regulated
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in multiple myeloma (MM) cell lines treated with both decitabine [PubChem=451668] TSA [PubChem=5562].

description_full:
[cell repeats an earlier one in this file: 1738 characters]


systematic_name: M17454
exact_source: Table 1S: higher in TamR tumor
source_species_code: HS
GEO_id: GSE7327
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in breast cancer tumors (formed by MCF-7 xenografts) resistant to tamoxifen [PubChem=5376].

description_full:
  Not all breast cancers respond to tamoxifen, and many develop resistance despite initial benefit. We used an in vivo model of estrogen receptor (ER)-positive breast cancer (MCF-7 xenografts) to investigate mechanisms of this resistance and develop strategies to circumvent it. Epidermal growth factor receptor (EGFR) and HER2, which were barely detected in control estrogen-treated tumors, increased slightly with tamoxifen and were markedly increased when tumors became resistant. Gefitinib, which inhibits EGFR/HER2, improved the antitumor effect of tamoxifen and delayed acquired resistance, but had no effect on estrogen-stimulated growth. Phosphorylated levels of p42/44 and p38 mitogen-activated protein kinases (both downstream of EGFR/HER2) were increased in the tamoxifen-resistant tumors and were suppressed by gefitinib. There was no apparent increase in phosphorylated AKT (also downstream of EGFR/HER2) in resistant tumors, but it was nonetheless suppressed by gefitinib. Phosphorylated insulin-like growth factor-IR (IGF-IR), which can interact with both EGFR and membrane ER, was elevated in the tamoxifen-resistant tumors compared with the sensitive group. However, ER-regulated gene products, including total IGF-IR itself and progesterone receptor, remained suppressed even at the time of acquired resistance. Tamoxifen's antagonism of classic ER genomic function was retained in these resistant tumors and even in tumors that overexpress HER2 (MCF-7 HER2/18) and are de novo tamoxifen-resistant. In conclusion, EGFR/HER2 may mediate tamoxifen resistance in ER-positive breast cancer despite continued suppression of ER genomic function by tamoxifen. IGF-IR expression remains dependent on ER but is activated in the tamoxifen-resistant tumors. This study provides a rationale to combine HER inhibitors with tamoxifen in clinical studies, even in tumors that do not initially overexpress EGFR/HER2.


systematic_name: M10319
exact_source: Table 2S
source_species_code: HS
GEO_id: GSE6956
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in prostate cancer samples from African-American patients compared to those from the European-American patients.

description_full:
[cell repeats an earlier one in this file: 1966 characters]


systematic_name: M11513
exact_source: Table 4S: Mean exp < 0
source_species_code: HS
GEO_id: GSE8430
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in MCF10A cells (breast cancer) grown at low (mesenchymal phenotype) compared to those grown at high (epithelial, basal-like phenotype) confluency.

description_full:
  Epithelial-mesenchymal transition (EMT) is defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. In carcinoma cells, EMT can be associated with increased aggressiveness, and invasive and metastatic potential. To assess the occurrence of EMT in human breast tumors, we conducted a tissue microarray-based immunohistochemical study in 479 invasive breast carcinomas and 12 carcinosarcomas using 28 different markers. Unsupervised hierarchical clustering of the tumors and statistical analysis showed that up-regulation of EMT markers (vimentin, smooth-muscle-actin, N-cadherin, and cadherin-11) and overexpression of proteins involved in extracellular matrix remodeling and invasion (SPARC, laminin, and fascin), together with reduction of characteristic epithelial markers (E-cadherin and cytokeratins), preferentially occur in breast tumors with the basal-like phenotype. Moreover, most breast carcinosarcomas also had a basal-like phenotype and showed expression of mesenchymal markers in their sarcomatous and epithelial components. To assess whether basal-like cells have intrinsic phenotypic plasticity for mesenchymal transition, we performed in vitro studies with the MCF10A cell line. In response to low cell density, MCF10A cells suffer spontaneous morphologic and phenotypic EMT-like changes, including cytoskeleton reorganization, vimentin and Slug up-regulation, cadherin switching, and diffuse cytosolic relocalization of the catenins. Moreover, these phenotypic changes are associated with modifications in the global genetic differentiation program characteristic of the EMT process. In summary, our data indicate that in breast tumors, EMT likely occurs within a specific genetic context, the basal phenotype, and suggests that this proclivity to mesenchymal transition may be related to the high aggressiveness and the characteristic metastatic spread of these tumors.


systematic_name: M13256
exact_source: Suppl. Data 1: hMSCs EWS-FLI1 repressed
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in mesenchymal stem cells (MSC) engineered to express EWS-FLI1 [GeneID=2130;2321] fusion protein.

description_full:
  Ewing's sarcoma family tumors (ESFT) express the EWS-FLI-1 fusion gene generated by the chromosomal translocation t(11;22)(q24;q12). Expression of the EWS-FLI-1 fusion protein in a permissive cellular environment is believed to play a key role in ESFT pathogenesis. However, EWS-FLI-1 induces growth arrest or apoptosis in differentiated primary cells, and the identity of permissive primary human cells that can support its expression and function has until now remained elusive. Here we show that expression of EWS-FLI-1 in human mesenchymal stem cells (hMSC) is not only stably maintained without inhibiting proliferation but also induces a gene expression profile bearing striking similarity to that of ESFT, including genes that are among the highest ESFT discriminators. Expression of EWS-FLI-1 in hMSCs may recapitulate the initial steps of Ewing's sarcoma development, allowing identification of genes that play an important role early in its pathogenesis. Among relevant candidate transcripts induced by EWS-FLI-1 in hMSCs, we found the polycomb group gene EZH2, which we show to play a critical role in Ewing's sarcoma growth. These observations are consistent with our recent findings using mouse mesenchymal progenitor cells and provide compelling evidence that hMSCs are candidate cells of origin of ESFT.


systematic_name: M7928
exact_source: Table 3S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in the MM1S cells (multiple myeloma) after treatment with aplidin [PubChem=44152164], a marine-derived compound with potential anti-cancer properties.

description_full:
  Despite recent progress in its treatment, multiple myeloma (MM) remains incurable, thus necessitating identification of novel anti-MM agents. We report that the marine-derived cyclodepsipeptide Aplidin exhibits, at clinically achievable concentrations, potent in vitro activity against primary MM tumor cells and a broad spectrum of human MM cell lines, including cells resistant to conventional (e.g., dexamethasone, alkylating agents, and anthracyclines) or novel (e.g., thalidomide and bortezomib) anti-MM agents. Aplidin is active against MM cells in the presence of proliferative/antiapoptotic cytokines or bone marrow stromal cells and has additive or synergistic effects with some of the established anti-MM agents. Mechanistically, a short in vitro exposure to Aplidin induces MM cell death, which involves activation of p38 and c-jun NH(2)-terminal kinase signaling, Fas/CD95 translocation to lipid rafts, and caspase activation. The anti-MM effect of Aplidin is associated with suppression of a constellation of proliferative/antiapoptotic genes (e.g., MYC, MYBL2, BUB1, MCM2, MCM4, MCM5, and survivin) and up-regulation of several potential regulators of apoptosis (including c-JUN, TRAIL, CASP9, and Smac). Aplidin exhibited in vivo anti-MM activity in a mouse xenograft model. The profile of the anti-MM activity of Aplidin in our preclinical models provided the framework for its clinical testing in MM, which has already provided favorable preliminary results.


systematic_name: M253
exact_source: Table 3S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes whose expression in suboptimally debulked ovarian tumors is associated with survival prognosis.

description_full:
[cell repeats an earlier one in this file: 1734 characters]


systematic_name: M19927
exact_source: Table 3S
source_species_code: HS
GEO_id: GSE10455
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in HCT116 cells (colon cancer) upon expression of MIR34B or MIR34C [GeneID=407041;407042] microRNAs.

description_full:
  Altered expression of microRNA (miRNA) is strongly implicated in cancer, and recent studies have shown that, in cancer, expression of some miRNAs cells is silenced in association with CpG island hypermethylation. To identify epigenetically silenced miRNAs in colorectal cancer (CRC), we screened for miRNAs induced in CRC cells by 5-aza-2'-deoxycytidine (DAC) treatment or DNA methyltransferase knockout. We found that miRNA-34b (miR-34b) and miR-34c, two components of the p53 network, are epigenetically silenced in CRC; that this down-regulation of miR-34b/c is associated with hypermethylation of the neighboring CpG island; and that DAC treatment rapidly restores miR-34b/c expression. Methylation of the miR-34b/c CpG island was frequently observed in CRC cell lines (nine of nine, 100%) and in primary CRC tumors (101 of 111, 90%), but not in normal colonic mucosa. Transfection of precursor miR-34b or miR-34c into CRC cells induced dramatic changes in the gene expression profile, and there was significant overlap between the genes down-regulated by miR-34b/c and those down-regulated by DAC. We also found that the miR-34b/c CpG island is a bidirectional promoter which drives expression of both miR-34b/c and B-cell translocation gene 4 (BTG4); that methylation of the CpG island is also associated with transcriptional silencing of BTG4; and that ectopic expression of BTG4 suppresses colony formation by CRC cells. Our results suggest that miR-34b/c and BTG4 are novel tumor suppressors in CRC and that the miR-34b/c CpG island, which bidirectionally regulates miR-34b/c and BTG4, is a frequent target of epigenetic silencing in CRC.


systematic_name: M4913
exact_source: Table 4S
source_species_code: RM
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in adipose tissue mesenchymal stem cells (ASC) vs bone marrow mesenchymal stem cells (rBMSC)

description_full:
  Mesenchymal stem cells (MSC) derived from bone marrow stem cells (BMSC) and adipose tissue stem cells (ASC) of humans and rhesus macaques were evaluated for their cell cycle properties during protracted culture in vitro. Human ASCs (hASC) and rhesus BMSCs (rBMSC) underwent significantly more total population doublings than human BMSCs (hBMSC) and rhesus ASCs (rASC). The cell cycle profile of all MSCs was altered as cultures aged. hMSCs underwent an increase in the frequency of cells in the S phase at P20 and P30. However, rhesus MSCs from both sources developed a distinct polyploid population of cells at P20, which progressed to aneuploidy by P30. Karyotype analysis of MSCs revealed the development of tetraploid or aneuploid karyotypes in the rhesus cells at P20 or P30. Analysis of the transcriptome of the MSCs from early and late passages revealed significant alterations in the patterns of gene expression (8.8% of the genes were differentially expressed in hBMSCs versus hASCs, and 5.5% in rBMSCs versus rASCs). Gene expression changes were much less evident within the same cell type as aging occurred (0.7% in hMSCs and 0.9% in rMSC). Gene ontology analysis showed that functions involved in protein catabolism and regulation of pol II transcription were overrepresented in rASCs, whereas the regulation of I kappa B/nuclear factor-kappaB cascade were overrepresented in hBMSCs. Functional analysis of genes that were differentially expressed in rASCs and hBMSCs revealed that pathways involved in cell cycle, cell cycle checkpoints, protein-ubiquitination, and apoptosis were altered.


systematic_name: M18107
exact_source: Table 1
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Atherosclerotic process genes whose coronary expression changed after darapladib [PubChem=9939609] treatment.

description_full:
  Increased lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity is associated with increased risk of cardiac events, but it is not known whether Lp-PLA(2) is a causative agent. Here we show that selective inhibition of Lp-PLA(2) with darapladib reduced development of advanced coronary atherosclerosis in diabetic and hypercholesterolemic swine. Darapladib markedly inhibited plasma and lesion Lp-PLA(2) activity and reduced lesion lysophosphatidylcholine content. Analysis of coronary gene expression showed that darapladib exerted a general anti-inflammatory action, substantially reducing the expression of 24 genes associated with macrophage and T lymphocyte functioning. Darapladib treatment resulted in a considerable decrease in plaque area and, notably, a markedly reduced necrotic core area and reduced medial destruction, resulting in fewer lesions with an unstable phenotype. These data show that selective inhibition of Lp-PLA(2) inhibits progression to advanced coronary atherosclerotic lesions and confirms a crucial role of vascular inflammation independent from hypercholesterolemia in the development of lesions implicated in the pathogenesis of myocardial infarction and stroke.


systematic_name: M1834
exact_source: Table 2S
source_species_code: HS
GEO_id: E-MEXP-167
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in freshly isolated CD31- [GeneID=5175] (stromal stem cells from adipose tissue) versus the CD31+ (non-stem) counterparts.

description_full:
  Stromal stem cells proliferate in vitro and may be differentiated along several lineages. Freshly isolated, these cells have been too few or insufficiently pure to be thoroughly characterized. Here, we have isolated two populations of CD45-CD34+CD105+ cells from human adipose tissue which could be separated based on expression of CD31. Compared with CD31+ cells, CD31- cells overexpressed transcripts associated with cell cycle quiescence and stemness, and transcripts involved in the biology of cartilage, bone, fat, muscle, and neural tissues. In contrast, CD31+ cells overexpressed transcripts associated with endothelium and the major histocompatibility complex class II complex. Clones of CD31- cells could be expanded in vitro and differentiated into cells with characteristics of bone, fat, and neural-like tissue. On culture, transcripts associated with cell cycle quiescence, stemness, certain cytokines and organ specific genes were down-regulated, whereas transcripts associated with signal transduction, cell adhesion, and cytoskeletal +CD105+CD31- cells from human adipose tissue have stromal stem cell properties which may make them useful for tissue engineering.


systematic_name: M1578
exact_source: Table 3S
source_species_code: HS
GEO_id: E-MEXP-167
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in freshly isolated CD31- [GeneID=5175] (stromal stem cells from adipose tissue) versus the CD31+ (non-stem) counterparts.

description_full:
  Stromal stem cells proliferate in vitro and may be differentiated along several lineages. Freshly isolated, these cells have been too few or insufficiently pure to be thoroughly characterized. Here, we have isolated two populations of CD45-CD34+CD105+ cells from human adipose tissue which could be separated based on expression of CD31. Compared with CD31+ cells, CD31- cells overexpressed transcripts associated with cell cycle quiescence and stemness, and transcripts involved in the biology of cartilage, bone, fat, muscle, and neural tissues. In contrast, CD31+ cells overexpressed transcripts associated with endothelium and the major histocompatibility complex class II complex. Clones of CD31- cells could be expanded in vitro and differentiated into cells with characteristics of bone, fat, and neural-like tissue. On culture, transcripts associated with cell cycle quiescence, stemness, certain cytokines and organ specific genes were down-regulated, whereas transcripts associated with signal transduction, cell adhesion, and cytoskeletal +CD105+CD31- cells from human adipose tissue have stromal stem cell properties which may make them useful for tissue engineering.


systematic_name: M17923
exact_source: Table 5S
source_species_code: HS
GEO_id: E-MEXP-168
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in cultured stromal stem cells from adipose tissue, compared to the freshly isolated cells.

description_full:
  Stromal stem cells proliferate in vitro and may be differentiated along several lineages. Freshly isolated, these cells have been too few or insufficiently pure to be thoroughly characterized. Here, we have isolated two populations of CD45-CD34+CD105+ cells from human adipose tissue which could be separated based on expression of CD31. Compared with CD31+ cells, CD31- cells overexpressed transcripts associated with cell cycle quiescence and stemness, and transcripts involved in the biology of cartilage, bone, fat, muscle, and neural tissues. In contrast, CD31+ cells overexpressed transcripts associated with endothelium and the major histocompatibility complex class II complex. Clones of CD31- cells could be expanded in vitro and differentiated into cells with characteristics of bone, fat, and neural-like tissue. On culture, transcripts associated with cell cycle quiescence, stemness, certain cytokines and organ specific genes were down-regulated, whereas transcripts associated with signal transduction, cell adhesion, and cytoskeletal +CD105+CD31- cells from human adipose tissue have stromal stem cell properties which may make them useful for tissue engineering.


systematic_name: M16336
exact_source: Table 1S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Up-regulated genes in MM1.S cells (multiple myeloma) treated with adaphostin [PubChem=387042], a tyrosine kinase inhibitor with anticancer properties.

description_full:
  Here we show the antimyeloma cytotoxicity of adaphostin and carried out expression profiling of adaphostin-treated multiple myeloma (MM) cells to identify its molecular targets. Surprisingly, c-Jun was the most up-regulated gene even at the earliest point of analysis (2 h). We also observed adaphostin-induced c-Abl cleavage in immunoblot analysis. Proteasome inhibitor bortezomib, but not melphalan or dexamethasone, induced similar effects, indicating unique agent-dependent mechanisms. Using caspase inhibitors, as well as caspase-resistant mutants of c-Abl (TM-c-Abl and D565A-Abl), we then showed that c-Abl cleavage in MM cells requires caspase activity. Importantly, both overexpression of the c-Abl fragment or c-Jun and knockdown of c-Abl and c-Jun expression by small interfering RNA confirmed that adaphostin-induced c-Jun up-regulation triggers downstream caspase-mediated c-Abl cleavage, inhibition of MM cell growth, and induction of apoptosis. Finally, our data suggest that this mechanism may not only be restricted to MM but may also be important in a broad range of malignancies including erythroleukemia and solid tumors.


systematic_name: M17621
exact_source: Table 4S
source_species_code: HS
GEO_id: GSE2241
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated 9 h after induction of HoxA5 [GeneID=3205] expression in a breast cancer cell line.

description_full:
  The homeobox gene HOXA5 encodes a transcription factor that has been shown to play important roles in embryogenesis, hematopoiesis, and tumorigenesis. In order to decipher downstream signaling pathways of HOXA5, we utilized oligonucleotide microarray analysis to identify genes that are differentially expressed in HOXA5-induced cells compared with uninduced cells. Comparative analysis of gene expression changes after 9 h of HOXA5 induction in Hs578T breast cancer cells identified 306 genes whose expression was modulated at least 2-fold. Ten of these 306 genes were also up-regulated by at least 2-fold at 6 h post-induction. The expression of all of these 10 genes was confirmed by semiquantitative reverse transcription-PCR. Among these 10 genes, which are most likely to be direct targets of HOXA5, we initiated an investigation into the pleiotrophin gene by first cloning its promoter. Transient transfection assays indicated that HOXA5 can specifically activate the pleiotrophin promoter. Promoter deletion, chromatin immunoprecipitation assay, and gel-shift assays were performed to show that HOXA5 can directly bind to one binding site on the pleiotrophin promoter. These data strongly suggest that microarray analysis can successfully identify many potential direct downstream genes of HOXA5. Further functional analysis of these targets will allow us to better understand the diverse functions of HOXA5 in embryonic development and tumorigenesis.


systematic_name: M7300
exact_source: Table 3S, 4S: cluster 2
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Selected genes up-regulated in response to the Ras inhibitor salirasib [PubChem=5469318] in a panel of cancer cell lines with constantly active HRAS [GeneID=3265].

description_full:
  Deregulation of Ras pathways results in complex abnormalities of multiple signaling cascades that contribute to human malignancies. Ras is therefore considered an appropriate target for cancer therapy. In light of the complexity of the deregulated Ras pathway, it is important to decipher at the molecular level the response of cancer cells to Ras inhibitors that would reregulate it. In the present study, we used gene expression profiling as a robust method for the global dissection of gene expression alterations that resulted from treatment with the Ras inhibitor S-farnesylthiosalicylic acid (FTS; salirasib). Use of a ranking-based procedure, combined with functional analysis and promoter sequence analysis, enabled us to decipher the common and most prominent patterns of the transcriptional response of five different human cancer cell lines to FTS. Remarkably, the analysis identified a distinctive core transcriptional response to FTS that was common to all cancer cell lines tested. This signature fits well to a recently described deregulated Ras pathway signature that predicted sensitivity to FTS. Taken together, these studies provide strong support for the conclusion that FTS specifically reregulates defective Ras pathways in human tumor cells. Ras pathway reregulation by FTS was manifested by repression of E2F-regulated and NF-Y-regulated genes and of the transcription factor FOS (all of which control cell proliferation), repression of survivin expression (which blocks apoptosis), and induction of activating transcription factor-regulated and Bach2-regulated genes (which participate in translation and stress responses). Our results suggest that cancer patients with deregulated Ras pathway tumors might benefit from FTS treatment.


systematic_name: M18806
exact_source: Table 1S: GemR/Parental
source_species_code: HS
GEO_id: GSE6914
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Down-regulated genes in Calu3 cells (non-small cell lung cancer, NSCLC) resistant to gemcitabine [PubChem=3461] which became up-regulated in response to bexarotene [PubChem=82146].

description_full:
  Acquired drug resistance is a major obstacle in cancer therapy. As for many other drugs, this is also the case for gemcitabine, a nucleoside analogue with activity against non-small cell lung cancer (NSCLC). Here, we evaluate the ability of bexarotene to modulate the acquisition and maintenance of gemcitabine resistance in Calu3 NSCLC models. In the prevention model, Calu3 cells treated repeatedly with gemcitabine alone gradually developed resistance. However, with inclusion of bexarotene, the cells remained chemosensitive. RNA analysis showed a strong increase of rrm1 (ribonucleotide reductase M1) expression in the resistant cells (Calu3-GemR), a gene known to be involved in gemcitabine resistance. In addition, the expression of genes surrounding the chromosomal location of rrm1 was increased, suggesting that resistance was due to gene amplification at the chr11 p15.5 locus. Analysis of genomic DNA confirmed that the rrm1 gene copy number was increased over 10-fold. Correspondingly, fluorescence in situ hybridization analysis of metaphase chromosomes showed an intrachromosomal amplification of the rrm1 locus. In the therapeutic model, bexarotene gradually resensitized Calu3-GemR cells to gemcitabine, reaching parental drug sensitivity after 10 treatment cycles. This was associated with a loss in rrm1 amplification. Corresponding with the in vitro data, xenograft tumors generated from the resistant cells did not respond to gemcitabine but were growth inhibited when bexarotene was added to the cytotoxic agent. The data indicate that bexarotene can resensitize gemcitabine-resistant tumor cells by reversing gene amplification. This suggests that bexarotene may have clinical utility in cancers where drug resistance by gene amplification is a major obstacle to successful therapy.


description_brief: Genes down-regulated in vascular smooth muscle cells (VSMC) by MAPK8 (JNK1) [GeneID=5599].
systematic_name: M1885
exact_source: Table 1S: J.I. < 0
source_species_code: RN
GEO_id: GSE2190
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_full:
  Abdominal aortic aneurysm (AAA) is a common disease among elderly people that, when surgical treatment is inapplicable, results in progressive expansion and rupture of the aorta with high mortality. Although nonsurgical treatment for AAA is much awaited, few options are available because its molecular pathogenesis remains elusive. Here, we identify JNK as a proximal signaling molecule in the pathogenesis of AAA. Human AAA tissue showed a high level of phosphorylated JNK. We show that JNK programs a gene expression pattern in different cell types that cooperatively enhances the degradation of the extracellular matrix while suppressing biosynthetic enzymes of the extracellular matrix. Selective inhibition of JNK in vivo not only prevented the development of AAA but also caused regression of established AAA in two mouse models. Thus, JNK promotes abnormal extracellular matrix metabolism in the tissue of AAA and may represent a therapeutic target.


description_brief: Genes up-regulated in T98G cells (glioblastoma) by TNC [GeneID=3371].
systematic_name: M988
exact_source: Table 1S: Fold Increase > 0
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Tenascin-C is an adhesion-modulating extracellular matrix molecule that is highly expressed in tumor stroma and stimulates tumor cell proliferation. Adhesion of T98G glioblastoma cells to a fibronectin substratum is inhibited by tenascin-C. To address the mechanism of action, we performed a RNA expression analysis of T89G cells grown in the presence or absence of tenascin-C and found that tenascin-C down-regulates tropomyosin-1. Upon overexpression of tropomyosin-1, cell spreading on a fibronectin/tenascin-C substratum was restored, indicating that tenascin-C destabilizes actin stress fibers through down-regulation of tropomyosin-1. Tenascin-C also increased the expression of the endothelin receptor type A and stimulated the corresponding mitogen-activated protein kinase signaling pathway, which triggers extracellular signal-regulated kinase 1/2 phosphorylation and c-Fos expression. Tenascin-C additionally caused down-regulation of the Wnt inhibitor Dickkopf 1. In consequence, Wnt signaling was enhanced through stabilization of beta-catenin and stimulated the expression of the beta-catenin target Id2. Finally, our in vivo data derived from astrocytoma tissue arrays link increased tenascin-C and Id2 expression with high malignancy. Because increased endothelin and Wnt signaling, as well as reduced tropomyosin-1 expression, are closely linked to transformation and tumorigenesis, we suggest that tenascin-C specifically modulates these signaling pathways to enhance proliferation of glioma cells.


description_brief: Genes up-regulated in peripheral blood monocytes by CSF2RB (GM-CSF) and IL4 [GeneID=1437;3565].
systematic_name: M12636
exact_source: Table 1S: GM4-DCs vs Ctrl FC >= 1
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Several hematopoietic growth factors, including interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1), promote the differentiation of tolerogenic dendritic cells (DCs). Hepatocyte growth factor (HGF) is a pleiotropic cytokine whose effects on human DC differentiation and function have not been investigated. Monocytes cultured with HGF (HGFMo) differentiated into accessory cells with DC-like morphology, released low amounts of IL-12p70 and up-regulated IL-10 both at the mRNA and at the protein level. Upon activation with HGFMo, allogeneic CD4+CD25- T cells expressed the T regulatory (Treg)-associated transcription factor FoxP3, proliferated poorly, and released high levels of IL-10. Interestingly, blockade of surface immunoglobulin-like transcript 3 (ILT3) on HGFMo or neutralization of secreted IL-10 translated into partial restoration of T-cell proliferation. Secondary stimulation of HGFMo-primed CD4+ T cells with immunogenic DCs differentiated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 from monocytes of the same donor resulted in measurable T-cell proliferation. HGFMo-primed CD4+ T cells significantly inhibited the proliferation of naive CD4+CD25- T cells in a cell-contact-dependent manner. Finally, DNA microarray analysis revealed a unique gene-expression profile of HGF-activated monocytes. Collectively, our findings point to a novel role for HGF in the regulation of monocyte/DC functions that might be exploited therapeutically.


systematic_name: M19971
exact_source: Table 1S: HGF vs GM4DCs FC >= 1
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in peripheral blood mononucleocytes by HGF [GeneID=3082] compared to those regulated by CSF2RB (GM-CSF) and IL4 [GeneID=1437;3565].

description_full:
[cell repeats an earlier one in this file: 1501 characters]


systematic_name: M13333
exact_source: Table 1S: HGF vs GM4DCs FC <= -1
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in peripheral blood mononucleocytes by HGF [GeneID=3082] compared to those regulated by CSF2RB (GM-CSF) and IL4 [GeneID=1437;3565].

description_full:
[cell repeats an earlier one in this file: 1501 characters]


systematic_name: M10573
exact_source: Table 6S
source_species_code: HS
GEO_id: GSE49200
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes that contributed maximally to the GSEA score of the up-regulated gene set from the KrasLA mouse model in two human lung cancer expression data sets comparing mutant vs normal KRAS [GeneID=3845].

description_full:
  Using advanced gene targeting methods, generating mouse models of cancer that accurately reproduce the genetic alterations present in human tumors is now relatively straightforward. The challenge is to determine to what extent such models faithfully mimic human disease with respect to the underlying molecular mechanisms that accompany tumor progression. Here we describe a method for comparing mouse models of cancer with human tumors using gene-expression profiling. We applied this method to the analysis of a model of Kras2-mediated lung cancer and found a good relationship to human lung adenocarcinoma, thereby validating the model. Furthermore, we found that whereas a gene-expression signature of KRAS2 activation was not identifiable when analyzing human tumors with known KRAS2 mutation status alone, integrating mouse and human data uncovered a gene-expression signature of KRAS2 mutation in human lung cancer. We confirmed the importance of this signature by gene-expression analysis of short hairpin RNA-mediated inhibition of oncogenic Kras2. These experiments identified both a pattern of gene expression indicative of KRAS2 mutation and potential effectors of oncogenic KRAS2 activity in human cancer. This approach provides a strategy for using genomic analysis of animal models to probe human disease.


systematic_name: M9639
exact_source: Table 3-bS
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in MDA-MB-231 cells (breast cancer) after knockdown of SATB1 [GeneID=6304] by RNAi.

description_full:
  Mechanisms underlying global changes in gene expression during tumour progression are poorly understood. SATB1 is a genome organizer that tethers multiple genomic loci and recruits chromatin-remodelling enzymes to regulate chromatin structure and gene expression. Here we show that SATB1 is expressed by aggressive breast cancer cells and its expression level has high prognostic significance (P < 0.0001), independent of lymph-node status. RNA-interference-mediated knockdown of SATB1 in highly aggressive (MDA-MB-231) cancer cells altered the expression of >1,000 genes, reversing tumorigenesis by restoring breast-like acinar polarity and inhibiting tumour growth and metastasis in vivo. Conversely, ectopic SATB1 expression in non-aggressive (SKBR3) cells led to gene expression patterns consistent with aggressive-tumour phenotypes, acquiring metastatic activity in vivo. SATB1 delineates specific epigenetic modifications at target gene loci, directly upregulating metastasis-associated genes while downregulating tumour-suppressor genes. SATB1 reprogrammes chromatin organization and the transcription profiles of breast tumours to promote growth and metastasis; this is a new mechanism of tumour progression.


systematic_name: M15491
exact_source: Table 3-cS
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in MDA-MB-231 cells (breast cancer) after knockdown of SATB1 [GeneID=6304] by RNAi.

description_full:
  Mechanisms underlying global changes in gene expression during tumour progression are poorly understood. SATB1 is a genome organizer that tethers multiple genomic loci and recruits chromatin-remodelling enzymes to regulate chromatin structure and gene expression. Here we show that SATB1 is expressed by aggressive breast cancer cells and its expression level has high prognostic significance (P < 0.0001), independent of lymph-node status. RNA-interference-mediated knockdown of SATB1 in highly aggressive (MDA-MB-231) cancer cells altered the expression of >1,000 genes, reversing tumorigenesis by restoring breast-like acinar polarity and inhibiting tumour growth and metastasis in vivo. Conversely, ectopic SATB1 expression in non-aggressive (SKBR3) cells led to gene expression patterns consistent with aggressive-tumour phenotypes, acquiring metastatic activity in vivo. SATB1 delineates specific epigenetic modifications at target gene loci, directly upregulating metastasis-associated genes while downregulating tumour-suppressor genes. SATB1 reprogrammes chromatin organization and the transcription profiles of breast tumours to promote growth and metastasis; this is a new mechanism of tumour progression.


systematic_name: M1919
exact_source: Supplementary Fig. 7C
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in MEF cells (embryonic fibroblast) with double knockout of the translation repressors 4EBP1 [GeneID=1978] and 4EBP2 [GeneID=1979].

description_full:
  Transcriptional activation of cytokines, such as type-I interferons (interferon (IFN)-alpha and IFN-beta), constitutes the first line of antiviral defence. Here we show that translational control is critical for induction of type-I IFN production. In mouse embryonic fibroblasts lacking the translational repressors 4E-BP1 and 4E-BP2, the threshold for eliciting type-I IFN production is lowered. Consequently, replication of encephalomyocarditis virus, vesicular stomatitis virus, influenza virus and Sindbis virus is markedly suppressed. Furthermore, mice with both 4E- and 4E-BP2 genes (also known as Eif4ebp1 and Eif4ebp2, respectively) knocked out are resistant to vesicular stomatitis virus infection, and this correlates with an enhanced type-I IFN production in plasmacytoid dendritic cells and the expression of IFN-regulated genes in the lungs. The enhanced type-I IFN response in 4E-BP1-/- 4E-BP2-/- double knockout mouse embryonic fibroblasts is caused by upregulation of interferon regulatory factor 7 (Irf7) messenger RNA translation. These findings highlight the role of 4E-BPs as negative regulators of type-I IFN production, via translational repression of Irf7 mRNA.


systematic_name: M215
exact_source: Table 1S-3S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Selected genes up-regulated in prostate tumors developed by transgenic mice overexpressing VAV3 [GeneID=10451] in prostate epithelium.

description_full:
  Our previous study revealed that Vav3 oncogene is overexpressed in human prostate cancer, activates androgen receptor (AR), and stimulates growth in prostate cancer cells. The purpose of this study is to further determine the potential role of Vav3 in prostate cancer development in genetically engineered mouse model. We generated Vav3 transgenic mice by targeted overexpression of a constitutive active Vav3 in the prostatic epithelium. We found that overexpression of Vav3 led to development of mouse prostatic intraepithelial neoplasia and prostate cancer at the age of as early as 3 months. The AR signaling axis and phosphatidylinositol 3-kinase-Akt signaling were elevated in the prostate glands of Vav3 transgenic mice. In addition to prostate cancer, Vav3 transgenic mice developed significant nonbacterial chronic prostatitis in the prostate gland with notable infiltration of lymphomononuclear cells (monocytes, lymphocytes, and plasma cells), which was associated with elevated incidence of prostate cancer. DNA microarray and signaling pathway analysis revealed that the top diseases and disorders were inflammatory diseases and cancer of the prostate gland in Vav3 transgenic mice. In vitro analysis showed that overexpression of Vav3 in prostate cancer cells enhanced nuclear factor-kappaB (NF-kappaB) activity, implicating an underlying mechanism of innate inflammatory response induced by elevated Vav3 activity. These data showed that Vav3 overexpression in the prostate epithelium enhanced both the AR signaling axis and NF-kappaB-mediated pathway, which potentially contributed to the development of nonbacterial prostatitis and prostate cancer.


systematic_name: M14437
exact_source: Supplementary Table E1
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Top 40 genes from cluster 5 of acute myeloid leukemia (AML) expression profile; 96% of the samples are FAB M4 or M5 subtype.

description_full:
[cell repeats an earlier one in this file: 1675 characters]


systematic_name: M5369
exact_source: Table 1S
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in atypical ductal hyperplastic tissues from patients with (ADHC) breast cancer vs those without the cancer (ADH).

description_full:
  Breast cancer is the second leading cause of cancer death for women in the United States. In 2005, about 215,000 cases of invasive breast cancer (IBC) and 50,000 cases of ductal carcinoma in situ will be diagnosed and 40,000 women will die of IBC in the US. Yet there is presently no molecular marker that can be used to detect a precancerous state or identify which premalignant lesions will develop into invasive breast cancer. Here we report the gene expression analysis of atypical ductal hyperplastic tissues from patients with and without a history of breast cancer. We identify MMP-1 as a candidate marker that may be useful for identification of breast lesions that can develop into cancer.


systematic_name: M8689
exact_source: Table 6S: Underexpressed in CTNNB1 class
source_species_code: HS
GEO_id: GSE9843
contributor: Yujin Hoshida
contrib_organization: Broad Institute
description_brief:
  Top 200 marker genes down-regulated in the 'CTNNB1' subclass of hepatocellular carcinoma (HCC); characterized by activated CTNNB1 [GeneID=1499].

description_full:
[cell repeats an earlier one in this file: 1805 characters]


systematic_name: M1047
exact_source: Table 4S: inv(16)-specific probe sets (471 probe sets)
source_species_code: HS
GEO_id: GSE2191
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes specifically expressed in samples from patients with pediatric acute myeloid leukemia (AML) bearing inv(16) translocation.

description_full:
[cell repeats an earlier one in this file: 980 characters]


systematic_name: M10290
exact_source: Table 1S
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in H1975 cells (non-small cell lung cancer, NSCLC) resistant to gefitinib [PubChem=123631] after treatment with EGFR inhibitor CL-387785 [PubChem=2776] for 24h.

description_full:
  Activating mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain determine responsiveness to EGFR tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer (NSCLC). The modulation of transcriptional pathways by mutant EGFR signaling is not fully understood. Previously, we and others identified a single base pair change leading to a threonine to methionine (T790M) amino acid alteration in the ATP-binding pocket of the EGFR as a common mechanism of acquired resistance. The gefitinib-resistant, T790M-mutant H1975 NSCLC cell line undergoes prominent growth arrest and apoptosis when treated with the irreversible EGFR inhibitor, CL-387,785. We did a transcriptional profiling study of mutant EGFR target genes that are differentially expressed in the resistant gefitinib-treated and the sensitive CL387,785-treated H1975 cells to identify the pivotal transcriptional changes in NSCLC with EGFR-activating mutations. We identified a small subset of early gene changes, including significant reduction of cyclin D1 as a result of EGFR inhibition by CL-387,785 but not by gefitinib. The reduction in cyclin D1 transcription was associated with subsequent suppression of E2F-responsive genes, consistent with proliferation arrest. Furthermore, cyclin D1 expression was higher in EGFR-mutant lung cancer cells compared with cells with wild-type EGFR. EGFR-mutant cells were routinely sensitive to the cyclin-dependent kinase inhibitor flavopiridol, confirming the functional relevance of the cyclin D axis. These studies suggest that cyclin D1 may contribute to the emergence of EGFR-driven tumorigenesis and can be an alternative target of therapy.


systematic_name: M5311
exact_source: Table 3S: Subtype=S1
source_species_code: HS
GEO_id: GSE10393
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes from 'subtype S1' signature of hepatocellular carcinoma (HCC): aberrant activation of the WNT signaling pathway.

description_full:
  Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, and prior attempts to develop genomic-based classification for HCC have yielded highly divergent results, indicating difficulty in identifying unified molecular anatomy. We performed a meta-analysis of gene expression profiles in data sets from eight independent patient cohorts across the world. In addition, aiming to establish the real world applicability of a classification system, we profiled 118 formalin-fixed, paraffin-embedded tissues from an additional patient cohort. A total of 603 patients were analyzed, representing the major etiologies of HCC (hepatitis B and C) collected from Western and Eastern countries. We observed three robust HCC subclasses (termed S1, S2, and S3), each correlated with clinical parameters such as tumor size, extent of cellular differentiation, and serum alpha-fetoprotein levels. An analysis of the components of the signatures indicated that S1 reflected aberrant activation of the WNT signaling pathway, S2 was characterized by proliferation as well as MYC and AKT activation, and S3 was associated with hepatocyte differentiation. Functional studies indicated that the WNT pathway activation signature characteristic of S1 tumors was not simply the result of beta-catenin mutation but rather was the result of transforming growth factor-beta activation, thus representing a new mechanism of WNT pathway activation in HCC. These experiments establish the first consensus classification framework for HCC based on gene expression profiles and highlight the power of integrating multiple data sets to define a robust molecular taxonomy of the disease.


description_brief: Genes whose promoters are bound by MYC [GeneID=4609], according to MYC Target Gene Database.
systematic_name: M15774
exact_source: http://www.myccancergene.org/site/mycTargetDB.asp
source_species_code: HS
contributor: Chi Dang
contrib_organization: Johns Hopkins University
description_full:
  We report a database of genes responsive to the Myc oncogenic transcription factor. The database Myc Target Gene prioritizes candidate target genes according to experimental evidence and clusters responsive genes into functional groups. We coupled the prioritization of target genes with phylogenetic sequence comparisons to predict c-Myc target binding sites, which are in turn validated by chromatin immunoprecipitation assays. This database is essential for the understanding of the genetic regulatory networks underlying the genesis of cancers.


systematic_name: M1999
exact_source: Table 4S: Mouse Entrez Gene ID
source_species_code: MM
GEO_id: GSE10423
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  The 'adult tissue stem' module: genes coordinately up-regulated in a compendium of adult tissue stem cells.

description_full:
  Self-renewal is a hallmark of stem cells and cancer, but existence of a shared stemness program remains controversial. Here, we construct a gene module map to systematically relate transcriptional programs in embryonic stem cells (ESCs), adult tissue stem cells, and human cancers. This map reveals two predominant gene modules that distinguish ESCs and adult tissue stem cells. The ESC-like transcriptional program is activated in diverse human epithelial cancers and strongly predicts metastasis and death. c-Myc, but not other oncogenes, is sufficient to reactivate the ESC-like program in normal and cancer cells. In primary human keratinocytes transformed by Ras and I kappa B alpha, c-Myc increases the fraction of tumor-initiating cells by 150-fold, enabling tumor formation and serial propagation with as few as 500 cells. c-Myc-enhanced tumor initiation is cell-autonomous and independent of genomic instability. Thus, activation of an ESC-like transcriptional program in differentiated adult cells may induce pathologic self-renewal characteristic of cancer stem cells.


systematic_name: M17951
exact_source: Table 3S: 1st PCA genes (+)
source_species_code: HS
GEO_id: GSE6481
contributor: Nikolaos Papanikolaou
contrib_organization: Aristoteles University of Thessaloniki
description_brief:
  Top 100 probe sets contrubuting to the positive side of the 1st principal component; predominantly associated with spindle cell and pleomorphic sarcoma samples.

description_full:
  In soft tissue sarcomas, the diagnosis of malignant fibrous histiocytoma (MFH) has been a very controversial issue, and MFH is now considered to be reclassified into pleomorphic subtypes of other sarcomas. To characterize MFH genetically, we used an oligonucleotide microarray to analyze gene expression in 105 samples from 10 types of soft tissue tumors. Spindle cell and pleomorphic sarcomas, such as dedifferentiated liposarcoma, myxofibrosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor (MPNST), fibrosarcoma and MFH, showed similar gene expression patterns compared to other tumors. Samples from those five sarcoma types could be classified into respective clusters based on gene expression by excluding MFH samples. We calculated distances between MFH samples and other five sarcoma types (dedifferentiated liposarcoma, myxofibrosarcoma, leiomyosarcoma, MPNST and fibrosarcoma) based on differentially expressed genes and evaluated similarities. Three of the 21 MFH samples showed marked similarities to one of the five sarcoma types, which were supported by histological findings. Although most of the remaining 18 MFH samples showed little or no histological resemblance to one of the five sarcoma types, 12 of them showed moderate similarities in terms of gene expression. These results explain the heterogeneity of MFH and show that the majority of MFHs could be reclassified into pleomorphic subtypes of other sarcomas. Taken together, gene expression profiling could be a useful tool to unveil the difference in the underlying molecular backgrounds, which leads to a rational taxonomy and diagnosis of a diverse group of soft tissue sarcomas.


systematic_name: M2094
exact_source: Table S3 PMLRAR common
source_species_code: HS
GEO_id: GSE18886
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes with promoters occupied by PML-RARA fusion [GeneID=5371,5914] protein in acute promyelocytic leukemia(APL) cells NB4 and two APL primary blasts, based on  Chip-seq data.

description_full:
  Many different molecular mechanisms have been associated with PML-RARalpha-dependent transformation of hematopoietic progenitors. Here, we identified high confidence PML-RARalpha binding sites in an acute promyelocytic leukemia (APL) cell line and in two APL primary blasts. We found colocalization of PML-RARalpha with RXR to the vast majority of these binding regions. Genome-wide epigenetic studies revealed that treatment with pharmacological doses of all-trans retinoic acid induces changes in H3 acetylation, but not H3K27me3, H3K9me3, or DNA methylation at the PML-RARalpha/RXR binding sites or at nearby target genes. Our results suggest that PML-RARalpha/RXR functions as a local chromatin modulator and that specific recruitment of histone deacetylase activities to genes important for hematopoietic differentiation, RAR signaling, and epigenetic control is crucial to its transforming potential.


systematic_name: M2099
exact_source: Table S6 downregulated genes
source_species_code: HS
GEO_id: GSE18886
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in NB4 cells (acute promyelocytic leukemia, APL) in response to tretinoin [PubChem=444795]; based on Chip-seq data.

description_full:
  Many different molecular mechanisms have been associated with PML-RARalpha-dependent transformation of hematopoietic progenitors. Here, we identified high confidence PML-RARalpha binding sites in an acute promyelocytic leukemia (APL) cell line and in two APL primary blasts. We found colocalization of PML-RARalpha with RXR to the vast majority of these binding regions. Genome-wide epigenetic studies revealed that treatment with pharmacological doses of all-trans retinoic acid induces changes in H3 acetylation, but not H3K27me3, H3K9me3, or DNA methylation at the PML-RARalpha/RXR binding sites or at nearby target genes. Our results suggest that PML-RARalpha/RXR functions as a local chromatin modulator and that specific recruitment of histone deacetylase activities to genes important for hematopoietic differentiation, RAR signaling, and epigenetic control is crucial to its transforming potential.


systematic_name: M2105
exact_source: Table 1S: correlation coefficient > 0
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes whose expression was significantly and positively correlated with the number of perineuronal oligodendrocytes in the layer III of BA9 brain region.

description_full:
[cell repeats an earlier one in this file: 1578 characters]


systematic_name: M2107
exact_source: Table 2S: correlation coefficient > 0
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes whose expression significantly and positively correlated with oligodendrocyte density in layer VI of BA9 brain region in patients with bipolar disorder.

description_full:
[cell repeats an earlier one in this file: 1578 characters]


systematic_name: M2110
exact_source: Table 3S: correlation coefficient > 0
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes whose expression significantly and positively correlated with the density of CALB1-positive [GeneID=793]  GABAergic interneurons in the BA9 brain region across all subjects with psychiatric disorders.

description_full:
[cell repeats an earlier one in this file: 1578 characters]


systematic_name: M2113
exact_source: Table 6S: correlation coefficient < 0
source_species_code: HS
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes whose expression in brain significantly and negatively correlated with the duration of all psychiatric disorders studied.

description_full:
[cell repeats an earlier one in this file: 1578 characters]


systematic_name: M2123
exact_source: Table 3S: Upregulated
source_species_code: HS
GEO_id: GSE17941
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Up-regulated genes in the cancer gene signature, representing a gene signature of cellular transformation.

description_full:
  Transcriptional profiling of two isogenic models of transformation identifies a gene signature linking cancer with inflammatory and metabolic diseases. In accord with this common transcriptional program, many drugs used for treatment of diabetes and cardiovascular diseases inhibit transformation and tumor growth. Unexpectedly, lipid metabolism genes are important for transformation and are upregulated in cancer tissues. As in atherosclerosis, oxidized LDL and its receptor OLR1 activate the inflammatory pathway through NF-kappaB, leading to transformation. OLR1 is important for maintaining the transformed state in developmentally diverse cancer cell lines and for tumor growth, suggesting a molecular connection between cancer and atherosclerosis. We suggest that the interplay between this common transcriptional program and cell-type-specific factors gives rise to phenotypically disparate human diseases.


systematic_name: M2125
exact_source: Table 2S: senescent_shRb_up
source_species_code: HS
GEO_id: GSE19899
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in senescent IMR90 cells (fibroblast) after knockdown of RB1 [GeneID=5925] by RNAi.

description_full:
  The RB protein family (RB, p107, and p130) has overlapping and compensatory functions in cell-cycle control. However, cancer-associated mutations are almost exclusively found in RB, implying that RB has a nonredundant role in tumor suppression. We demonstrate that RB preferentially associates with E2F target genes involved in DNA replication and is uniquely required to repress these genes during senescence but not other growth states. Consequently, RB loss leads to inappropriate DNA synthesis following a senescence trigger and, together with disruption of a p21-mediated cell-cycle checkpoint, enables extensive proliferation and rampant genomic instability. Our results identify a nonredundant RB effector function that may contribute to tumor suppression and reveal how loss of RB and p53 cooperate to bypass senescence.


systematic_name: M2128
exact_source: Table 2S: growing_shRb_up
source_species_code: HS
GEO_id: GSE19899
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in growing IMR90 cells (fibroblast) after knockdown of RB1 [GeneID=5925] by RNAi.

description_full:
  The RB protein family (RB, p107, and p130) has overlapping and compensatory functions in cell-cycle control. However, cancer-associated mutations are almost exclusively found in RB, implying that RB has a nonredundant role in tumor suppression. We demonstrate that RB preferentially associates with E2F target genes involved in DNA replication and is uniquely required to repress these genes during senescence but not other growth states. Consequently, RB loss leads to inappropriate DNA synthesis following a senescence trigger and, together with disruption of a p21-mediated cell-cycle checkpoint, enables extensive proliferation and rampant genomic instability. Our results identify a nonredundant RB effector function that may contribute to tumor suppression and reveal how loss of RB and p53 cooperate to bypass senescence.


systematic_name: M2129
exact_source: Table 2S: confluent_shRb_up
source_species_code: HS
GEO_id: GSE19899
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in confluent IMR90 cells (fibroblast) after knockdown of RB1 [GeneID=5925] by RNAi.

description_full:
[cell repeats an earlier one in this file: 828 characters]


systematic_name: M2140
exact_source: Fig 5SJ: personal communication
source_species_code: HS
GEO_id: GSE20381
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in SKOV3ip1 cells (ovarian cancer) upon knockdown of EZH2 [GeneID=2146] by RNAi.

description_full:
  Although VEGF-targeted therapies are showing promise, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homolog 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome. The increase in endothelial EZH2 is a direct result of VEGF stimulation by a paracrine circuit that promotes angiogenesis by methylating and silencing vasohibin1 (vash1). Ezh2 silencing in the tumor-associated endothelial cells inhibited angiogenesis mediated by reactivation of VASH1, and reduced ovarian cancer growth, which is further enhanced in combination with ezh2 silencing in tumor cells. Collectively, these data support the potential for targeting ezh2 as an important therapeutic approach.


