Polycomb group RING finger proteins 3/5 activate transcription via an interaction with the pluripotency factor Tex10 in embryonic stem cells
Polycomb group RING finger proteins 3/5 activate transcription via an interaction with the pluripotency factor Tex10 in embryonic stem cells
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多梳族环指蛋白 3/5 通过与胚胎干细胞中的多能因子 Tex10 相互作用激活转录
DOI：
10.1074/jbc.m117.804054
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Jinzhong Qin
中科院分区：
文献类型：
--
作者：
Wukui Zhao;Yikai Huang;Jingzi Zhang;Mengjie Liu;Haijing Ji;Congcong Wang;Ning Cao;Chaojun Li;Yin Xia;Qing Jiang;Jinzhong Qin
多梳族 (PcG) 蛋白是表观遗传转录抑制因子，可协调众多发育过程，并参与胚胎干 (ES) 细胞状态的维持。最近的证据表明，PcG 蛋白的一个子集在某些细胞环境中参与转录激活，但如何发挥这种特性仍然很大程度上未知。在这里，我们使用 CRISPR-Cas9 技术生成了对多梳组环指蛋白 3 (Pcgf3) 和 Pcgf5 进行单一或联合破坏的 ES 细胞。我们报告说，尽管这些突变细胞保持了自我更新和集落形成能力，但它们在体外和体内的中胚层分化中表现出严重的缺陷。使用 RNA-seq 分析具有单一或组合 Pcgf3/5 缺陷的 ES 细胞的转录谱，我们发现与相关多梳抑制复合物 1 (PRC1) 在基因抑制中的典型作用相反，Pcgf3/5 主要充当转录激活剂，驱动许多参与中胚层分化的基因的表达。蛋白质组学方法和启动子占据分析有助于建立扩展的 Pcgf3/5 相互作用组，并鉴定了几种新型 Pcgf3/5 相互作用子。其中包括睾丸表达的 10 (Tex10)，它可能通过转录共激活因子 p300 直接促进转录激活。此外，ES细胞中Pcgf3/5的缺失大大减少了Tex10和p300在靶基因上的占据。最后，我们证明 Pcgf3/5 对于调节 ES 细胞中组蛋白修饰剂 H2AK119ub1 的整体水平至关重要。我们的研究结果表明 Pcgf3/5 是与 ES 细胞中的 Tex10 和 p300 相互作用的转录激活剂，并指出 Pcgf3/5 在多能性维持中的冗余活性。
Polycomb group (PcG) proteins are epigenetic transcriptional repressors that orchestrate numerous developmental processes and have been implicated in the maintenance of embryonic stem (ES) cell state. More recent evidence suggests that a subset of PcG proteins engages in transcriptional activation in some cellular contexts, but how this property is exerted remains largely unknown. Here, we generated ES cells with single or combined disruption of polycomb group RING finger protein 3 (Pcgf3) and Pcgf5 with the CRISPR-Cas9 technique. We report that although these mutant cells maintained their self-renewal and colony-forming capacity, they displayed severe defects in mesoderm differentiation in vitro and in vivo. Using RNA-seq to analyze transcriptional profiles of ES cells with single or combined Pcgf3/5 deficiencies, we found that in contrast to the canonical role of the related polycomb repressive complex 1 (PRC1) in gene repression, Pcgf3/5 mainly function as transcriptional activators driving expression of many genes involved in mesoderm differentiation. Proteomic approaches and promoter occupancy analyses helped to establish an extended Pcgf3/5 interactome and identified several novel Pcgf3/5 interactors. These included testis-expressed 10 (Tex10), which may directly contribute to transcriptional activation via the transcriptional co-activator p300. Furthermore, Pcgf3/5 deletion in ES cells substantially reduced the occupancy of Tex10 and p300 at target genes. Finally, we demonstrated that Pcgf3/5 are essential for regulating global levels of the histone modifier H2AK119ub1 in ES cells. Our findings establish Pcgf3/5 as transcriptional activators that interact with Tex10 and p300 in ES cells and point to redundant activity of Pcgf3/5 in pluripotency maintenance.
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DOI：
10.1126/science.aal2512
发表时间：
2017-06-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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影响因子：
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通讯作者：
Tevosian, Sergei G.
影响因子：
3.3
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Castle CD;Cassimere EK;Denicourt C
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Denicourt C
影响因子：
23.9
作者：
Qin, Jinzhong;Whyte, Warren A.;Anderssen, Endre;Apostolou, Effie;Chen, Hsu-Hsin;Akbarian, Schahram;Bronson, Roderick T.;Hochedlinger, Konrad;Ramaswamy, Sridhar;Young, Richard A.;Hock, Hanno
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DOI：
10.1016/j.gep.2015.07.002
发表时间：
2015-09
期刊：
Gene expression patterns : GEP
影响因子：
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