Polycomb-like 2 associates with PRC2 and regulates transcriptional networks during mouse embryonic stem cell self-renewal and differentiation.
Polycomb-like 2 associates with PRC2 and regulates transcriptional networks during mouse embryonic stem cell self-renewal and differentiation.
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DOI：
10.1016/j.stem.2009.12.014
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发表时间：
2010-02-05
期刊：
影响因子：
23.9
通讯作者：
Stanford WL
中科院分区：
文献类型：
--
作者：
Walker E;Chang WY;Hunkapiller J;Cagney G;Garcha K;Torchia J;Krogan NJ;Reiter JF;Stanford WL
Polycomb group（PcG）蛋白是一种保守的表观遗传转录抑制因子，它控制着许多发育基因的表达，最近被发现参与调控胚胎干细胞（ESC）的命运。我们在全基因组筛选自我更新和多能性调节因子中鉴定了PcG蛋白PCL2（polycomb-like 2），并预测它将在小鼠ESC命运决定中发挥重要作用。使用多种生化策略，我们提供的证据表明，PCL2是一个多梳抑制复合物2（PRC2）相关蛋白在小鼠胚胎干细胞。敲低胚胎干细胞中的Pcl2导致自我更新特性增强、分化缺陷和组蛋白甲基化模式改变。整合全局基因表达和启动子占用分析，使我们能够确定PCL2和PRC2的转录靶点和草案的监管网络。我们描述了PCL2在未分化胚胎干细胞中调节胚胎干细胞自我更新基因转录的作用，以及在早期承诺和分化过程中的发育调节因子。
Polycomb group (PcG) proteins are conserved epigenetic transcriptional repressors that control numerous developmental gene expression programs and have recently been implicated in modulating embryonic stem cell (ESC) fate. We identified the PcG protein PCL2 (polycomb-like 2) in a genome-wide screen for regulators of self-renewal and pluripotency and predicted that it would play an important role in mouse ESC fate determination. Using multiple biochemical strategies, we provide evidence that PCL2 is a Polycomb Repressive Complex 2 (PRC2)-associated protein in mouse ESCs. Knockdown of Pcl2 in ESCs resulted in heightened self-renewal characteristics, defects in differentiation and altered patterns of histone methylation. Integration of global gene expression and promoter occupancy analyses allowed us to identify PCL2 and PRC2 transcriptional targets and draft regulatory networks. We describe the role of PCL2 in both modulating transcription of ESC self-renewal genes in undifferentiated ESCs as well as developmental regulators during early commitment and differentiation.
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影响因子：
1.5
作者：
Furuyama, T;Tie, F;Harte, PJ
通讯作者：
Harte, PJ
DOI：
10.1073/pnas.0409875102
发表时间：
2005-02-08
影响因子：
11.1
作者：
Kuzmichev, A;Margueron, R;Reinberg, D
通讯作者：
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影响因子：
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作者：
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通讯作者：
Krutchinsky, Andrew N.
影响因子：
64.5
作者：
Czermin, B;Melfi, R;Pirrotta, V
通讯作者：
Pirrotta, V
影响因子：
64.5
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
通讯作者：
Orkin, Stuart H.