Combinatorial Control of Recruitment of a Variant PRC1.6 Complex in Embryonic Stem Cells
Combinatorial Control of Recruitment of a Variant PRC1.6 Complex in Embryonic Stem Cells
复制标题
胚胎干细胞中变体 PRC1.6 复合物募集的组合控制。
DOI：
10.1016/j.celrep.2018.02.072
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发表时间：
2018-03-13
期刊：
影响因子：
8.8
通讯作者：
Qin, Jinzhong
中科院分区：
文献类型：
--
作者：
Huang, Yikai;Zhao, Wukui;Qin, Jinzhong
虽然遗传数据表明，多梳组蛋白（PcG）是中央染色质修饰剂和阻遏物，已涉及控制胚胎干细胞（ESC）的多能性，PcG复合物募集的精确机制仍然难以捉摸，特别是在哺乳动物中。我们现在报告，L3mbtl2的第一和第二MBT重复序列是重要的结构和功能特征，对于L3mbtl2介导的PRC1.6复合物向靶启动子的募集是必要的和足够的。有趣的是，L3mbtl2的该区域具有在果蝇Sfmbt中也存在的进化上保守的Pho结合口袋，并且该口袋内的关键残基的突变完全废除了其与靶启动子的相互作用。此外，在复合物的单个组分（L3mbtl2、Pcgf6和Max）损失后观察到PRC1.6染色质占用率降低。我们的研究结果表明，非典型PRC1.6复合物在ESCs中的募集可能是L3mbtl2与复合物的多个组分相互作用的结果。
Though genetic data suggest that Polycomb group proteins (PcGs) are central chromatin modifiers and repressors that have been implicated in control of embryonic stem cell (ESC) pluripotency, the precise mechanism of PcG complex recruitment remains elusive, especially in mammals. We now report that the first and second MBT repeats of L3mbtl2 are important structural and functional features that are necessary and sufficient for L3mbtl2-mediated recruitment of PRC1.6 complex to target promoters. Interestingly, this region of L3mbtl2 harbors the evolutionarily conserved Pho-binding pocket also present in Drosophila Sfmbt, and mutation of the critical residues within this pocket completely abolishes its interaction with target promoters. Additionally, decreased PRC1.6 chromatin occupancy was observed following loss of individual components (L3mbtl2, Pcgf6, and Max) of the complex. Our findings suggest that the recruitment of noncanonical PRC1.6 complex in ESCs might be the result of L3mbtl2's interaction with multiple components of the complex.