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Polycomb-like proteins link the PRC2 complex to CpG islands

  • [设施]:上海设施
  • [期刊/会议名称]:Nature
  • [摘要]:The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression and has essential roles in various biological processes including the maintenance of cell identity and proper differentiation. Polycomb-like (PCL) proteins, such as PHF1, MTF2 and PHF19, are PRC2-associated factors that form subcomplexes with PRC2 core components, and have been proposed to modulate the enzymatic activity of PRC2 or the recruitment of PRC2 to specific genomic loci. Mammalian PRC2-binding sites are enriched in CG content, which correlates with CpG islands that display a low level of DNA methylation. However, the mechanism of PRC2 recruitment to CpG islands is not fully understood. Here we solve the crystal structures of the N-terminal domains of PHF1 and MTF2 with bound CpG-containing DNAs in the presence of H3K36me3-containing histone peptides. We show that the extended homologous regions of both proteins fold into a winged-helix structure, which specifically binds to the unmethylated CpG motif but in a completely different manner from the canonical wingedhelix DNA recognition motif. We also show that the PCL extended homologous domains are required for efficient recruitment of PRC2 to CpG island-containing promoters in mouse embryonic stem cells. Our research provides the first, to our knowledge, direct evidence to demonstrate that PCL proteins are crucial for PRC2 recruitment to CpG islands, and further clarifies the roles of these proteins in transcriptional regulation in vivo.
  • [发表日期]:2017
  • [第一作者]:Haojie Li
  • [第一作者单位]:Beijing Normal University
  • [通讯作者]:Zhanxin Wang
  • [通讯作者单位]:Beijing Normal University
  • [论文类型]:0
  • [期刊分类]:SCI1区
  • [学科分类]:分子生物学_遗传学
  • [影响因子]:40.137
  • [关键词]:PCL; PRC2; CpG islands; Crystal structure; recruitment
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