Human Gene Set: KONDO_EZH2_TARGETS


Standard name KONDO_EZH2_TARGETS
Systematic name M5301
Brief description Genes up-regulated in PC3 cells (prostate cancer) after EZH2 [GeneID=2146] knockdown by RNAi.
Full description or abstract Epigenetic silencing in cancer cells is mediated by at least two distinct histone modifications, polycomb-based histone H3 lysine 27 trimethylation (H3K27triM) and H3K9 dimethylation. The relationship between DNA hypermethylation and these histone modifications is not completely understood. Using chromatin immunoprecipitation microarrays (ChIP-chip) in prostate cancer cells compared to normal prostate, we found that up to 5% of promoters (16% CpG islands and 84% non-CpG islands) were enriched with H3K27triM. These genes were silenced specifically in prostate cancer, and those CpG islands affected showed low levels of DNA methylation. Downregulation of the EZH2 histone methyltransferase restored expression of the H3K27triM target genes alone or in synergy with histone deacetylase inhibition, without affecting promoter DNA methylation, and with no effect on the expression of genes silenced by DNA hypermethylation. These data establish EZH2-mediated H3K27triM as a mechanism of tumor-suppressor gene silencing in cancer that is potentially independent of promoter DNA methylation.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18488029   Authors: Kondo Y,Shen L,Cheng AS,Ahmed S,Boumber Y,Charo C,Yamochi T,Urano T,Furukawa K,Kwabi-Addo B,Gold DL,Sekido Y,Huang TH,Issa JP
Exact source Table 4S
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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Version history 3.0: First introduced

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