Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation
作者： Yutaka Kondo , Lanlan Shen , Alfred S Cheng , Saira Ahmed , Yanis Boumber
DOI: 10.1038/NG.159
关键词:
摘要: Epigenetic silencing in cancer cells is mediated by at least two distinct histone modifications, polycomb-based H3 lysine 27 trimethylation (H3K27triM) and H3K9 dimethylation. The relationship between DNA hypermethylation these modifications not completely understood. Using chromatin immunoprecipitation microarrays (ChIP-chip) prostate compared to normal prostate, we found that up 5% of promoters (16% CpG islands 84% non-CpG islands) were enriched with H3K27triM. These genes silenced specifically cancer, those affected showed low levels methylation. Downregulation the EZH2 methyltransferase restored expression H3K27triM target alone or synergy deacetylase inhibition, without affecting promoter methylation, no effect on hypermethylation. data establish EZH2-mediated as a mechanism tumor-suppressor gene potentially independent
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