Essential Role for Polycomb Group Protein Pcgf6 in Embryonic Stem Cell Maintenance and a Noncanonical Polycomb Repressive Complex 1 (PRC1) Integrity.
Essential Role for Polycomb Group Protein Pcgf6 in Embryonic Stem Cell Maintenance and a Noncanonical Polycomb Repressive Complex 1 (PRC1) Integrity.
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Polycomb 组蛋白 Pcgf6 在胚胎干细胞维持和非经典 Polycomb 抑制复合物 1 (PRC1) 完整性中的重要作用。
DOI：
10.1074/jbc.m116.763961
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发表时间：
2017-02-17
影响因子：
4.8
通讯作者：
Qin, Jinzhong
中科院分区：
文献类型：
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作者：
Zhao, Wukui;Tong, Huan;Qin, Jinzhong
Polycomb group （PcG）蛋白在控制与胚胎发育、分化和细胞命运决定有关的关键基因的表达中起着重要作用。新出现的证据表明，Polycomb抑制复合物1 （PRC1）是由六个Polycomb组RING finger protein （Pcgf）类似物定义的，Pcgf蛋白可以组装成非规范的PRC1复合物。然而，对于不同组成的非典型PRC1在维持多能细胞状态中的精确机制知之甚少。本研究通过CRISPR-Cas9破坏小鼠胚胎干细胞中的Pcgf基因，发现Pcgf6缺失的胚胎干细胞在自我更新和分化方面存在严重缺陷。此外，Pcgf6通过组装非规范PRC1复合体PRC1.6来调节主要参与分化和精子发生的基因。值得注意的是，Pcgf6缺失导致PRC1.6与靶基因的结合显著减少，而H2AK119ub1没有丢失。因此，Pcgf6对于将PRC1.6募集到染色质上至关重要。我们的研究结果揭示了一个以前未被表征的与PRC1.6复合物相关的H2AK119ub1独立染色质组装。
The Polycomb group (PcG) proteins have an important role in controlling the expression of key genes implicated in embryonic development, differentiation, and decision of cell fates. Emerging evidence suggests that Polycomb repressive complexes 1 (PRC1) is defined by the six Polycomb group RING finger protein (Pcgf) paralogs, and Pcgf proteins can assemble into noncanonical PRC1 complexes. However, little is known about the precise mechanisms of differently composed noncanonical PRC1 in the maintenance of the pluripotent cell state. Here we disrupt the Pcgf genes in mouse embryonic stem cells by CRISPR-Cas9 and find Pcgf6 null embryonic stem cells display severe defects in self-renewal and differentiation. Furthermore, Pcgf6 regulates genes mostly involved in differentiation and spermatogenesis by assembling a noncanonical PRC1 complex PRC1.6. Notably, Pcgf6 deletion causes a dramatic decrease in PRC1.6 binding to target genes and no loss of H2AK119ub1. Thus, Pcgf6 is essential for recruitment of PRC1.6 to chromatin. Our results reveal a previously uncharacterized, H2AK119ub1 independent chromatin assembly associated with PRC1.6 complex.