Polycomb Group Protein Pcgf6 Acts as a Master Regulator to Maintain Embryonic Stem Cell Identity.
Polycomb Group Protein Pcgf6 Acts as a Master Regulator to Maintain Embryonic Stem Cell Identity.
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DOI：
10.1038/srep26899
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发表时间：
2016-06-01
影响因子：
4.6
通讯作者：
Rana TM
中科院分区：
文献类型：
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作者：
Yang CS;Chang KY;Dang J;Rana TM
多梳抑制复合物 1 (PRC1) 是一种多亚基复合物，在基因表达的表观遗传调节中发挥着关键作用。在这里，我们表明 PRC1 成分多梳组环指 6 (Pcgf6) 是维持胚胎干细胞 (ESC) 身份所必需的。与经典 PRC1 不同，Pcgf6 作为转录的正调节因子，主要与带有活性染色质标记的启动子结合。 Pcgf6 在 ESC 中高水平表达，敲低会降低核心 ESC 调节因子 Oct4、Sox2 和 Nanog 的表达。相反，Pcgf6 过度表达会阻止这些因子的下调并损害分化。此外，Pcgf6 增强了小鼠和人类体细胞的重编程。 Pcgf6 的基因组结合谱与 trithorax 组蛋白的基因组结合谱高度相似，但与 PRC1 或 PRC2 复合物不同，表明 Pcgf6 在 ESC 中的功能非典型。我们的数据揭示了 Pcgf6 在直接调节 Oct4、Nanog、Sox2 和 Lin28 表达以维持 ESC 身份方面的新作用。
The polycomb repressive complex 1 (PRC1) is a multi-subunit complex that plays critical roles in the epigenetic modulation of gene expression. Here, we show that the PRC1 component polycomb group ring finger 6 (Pcgf6) is required to maintain embryonic stem cell (ESC) identity. In contrast to canonical PRC1, Pcgf6 acts as a positive regulator of transcription and binds predominantly to promoters bearing active chromatin marks. Pcgf6 is expressed at high levels in ESCs, and knockdown reduces the expression of the core ESC regulators Oct4, Sox2, and Nanog. Conversely, Pcgf6 overexpression prevents downregulation of these factors and impairs differentiation. In addition, Pcgf6 enhanced reprogramming in both mouse and human somatic cells. The genomic binding profile of Pcgf6 is highly similar to that of trithorax group proteins, but not of PRC1 or PRC2 complexes, suggesting that Pcgf6 functions atypically in ESCs. Our data reveal novel roles for Pcgf6 in directly regulating Oct4, Nanog, Sox2, and Lin28 expression to maintain ESC identity.