A Dimeric Structural Scaffold for PRC2-PCL Targeting to CpG Island Chromatin.,Molecular Cell

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A Dimeric Structural Scaffold for PRC2-PCL Targeting to CpG Island Chromatin.
Molecular Cell ( IF 14.5 ) Pub Date : 2020-01-13 , DOI: 10.1016/j.molcel.2019.12.019
Siming Chen ₁ , Lianying Jiao ₁ , Xiuli Liu ₁ , Xin Yang ₁ , Xin Liu ₁

Affiliation

Diverse accessory subunits are involved in the recruitment of polycomb repressive complex 2 (PRC2) to CpG island (CGI) chromatin. Here we report the crystal structure of a SUZ12-RBBP4 complex bound to fragments of the accessory subunits PHF19 and JARID2. Unexpectedly, this complex adopts a dimeric structural architecture, accounting for PRC2 self-association that has long been implicated. The intrinsic PRC2 dimer is formed via domain swapping involving RBBP4 and the unique C2 domain of SUZ12. MTF2 and PHF19 associate with PRC2 at around the dimer interface and stabilize the dimer. Conversely, AEBP2 binding results in a drastic movement of the C2 domain, disrupting the intrinsic PRC2 dimer. PRC2 dimerization enhances CGI DNA binding by PCLs in pairs in vitro, reminiscent of the widespread phenomenon of transcription factor dimerization in active transcription. Loss of PRC2 dimerization impairs histone H3K27 trimethylation (H3K27me3) on chromatin at developmental gene loci in mouse embryonic stem cells.

中文翻译：

针对 CpG 岛染色质的 PRC2-PCL 的二聚结构支架。

多种辅助亚基参与多梳抑制复合物 2 (PRC2) 向 CpG 岛 (CGI) 染色质的募集。在这里，我们报告了与辅助亚基 PHF19 和 JARID2 片段结合的 SUZ12-RBBP4 复合物的晶体结构。出乎意料的是，这个复合物采用了二聚体结构，解释了长期以来一直受到牵连的 PRC2 自缔合。内在的 PRC2 二聚体是通过涉及 RBBP4 和 SUZ12 独特的 C2 结构域的结构域交换而形成的。MTF2 和 PHF19 在二聚体界面周围与 PRC2 结合并稳定二聚体。相反，AEBP2 结合会导致 C2 结构域剧烈移动，破坏内在的 PRC2 二聚体。PRC2二聚化在体外增强了PCL对CGI DNA的结合，这让人想起活性转录中转录因子二聚化的普遍现象。PRC2 二聚化的缺失会损害小鼠胚胎干细胞发育基因位点染色质上的组蛋白 H3K27 三甲基化 (H3K27me3)。

更新日期：2020-01-17

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