北師大青千王佔新Nature：PCL家族蛋白是連接PRC2與CpG島的紐帶

本文轉載自青塔

北京師範大學青年千人王佔新團隊最新Nature

北京時間2017年9月7日，國際頂級學術期刊Nature（《自然》）在線刊登了北京師範大學生命科學學院細胞增殖及調控生物學教育部重點實驗室王佔新教授課題組發表的題為「Polycomb-like proteins link the PRC2 complex to CpG islands」的文章，報道了該研究組關於PCL家族蛋白調控PRC2複合物在染色質上定位的機理研究上的突破性進展。

該研究首次發現並證實了PCL家族蛋白是連接PRC2與CpG島的紐帶，該工作為PRC2複合物在染色質上CpG島特異的招募提供了直接的實驗證據，解決了困惑人們多年的關於PRC2在染色質上選擇性定位的這一重要問題，為進一步理解PCL家族蛋白在PRC2複合物中的生理功能，以及靶向與PRC2相關疾病開闢了一個全新的思路。

該研究由北京師範大學生命科學學院青年千人王佔新教授領導的團隊經歷4年多的辛苦工作得以完成，參與合作的實驗室有哈佛大學醫學院的施揚教授實驗室、Martha Bulyk教授實驗室和Memorial Sloan-Kettering Cancer Center的Dinshaw J. Patel教授實驗室。王佔新實驗室的博士生李豪傑和蔣君翊以及哈佛大學醫學院施揚教授實驗室的博士後Robert Liefke為本文的共同第一作者，王佔新教授為通訊作者，北京師範大學生命科學學院細胞增殖及調控生物學教育部重點實驗室為第一完成單位。鏈接：

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature23881.html

以上轉載自青塔

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 sub-complexes 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 winged-helix 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.

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