Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
Cell Stem Cell. 2010 Feb 5;6(2):153-66. doi: 10.1016/j.stem.2009.12.014.
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.
多梳组 (PcG) 蛋白是保守的表观遗传转录抑制剂，可控制众多发育基因表达程序，最近还被认为可调节胚胎干细胞 (ESC) 命运。我们在一个自我更新和多能性调控因子的全基因组筛选中鉴定出 PcG 蛋白 PCL2（多梳样蛋白 2），并预测它将在小鼠 ESC 命运决定中发挥重要作用。我们使用多种生化策略提供证据表明，PCL2 是小鼠 ESCs 中多梳抑制复合物 2 (PRC2) 的相关蛋白。在 ESCs 中敲低 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据分析使我们能够鉴定 PCL2 和 PRC2 的转录靶标，并起草调控网络。我们描述了 PCL2 在调节未分化 ESCs 中 ESC 自我更新基因以及早期分化和分化过程中的发育调节剂的转录中的作用。
