Centre for Genomic Regulation and UPF, Dr. Aiguader, 88, 08003 Barcelona, Spain.
Cell Stem Cell. 2012 Jan 6;10(1):47-62. doi: 10.1016/j.stem.2011.12.006.
Polycomb group proteins are essential regulators of cell fate decisions during embryogenesis. In mammals, at least five different Cbx proteins (Cbx2, Cbx4, Cbx6, Cbx7, and Cbx8) are known to associate with the core Polycomb repressive complex 1 (PRC1). Here we show that pluripotency and differentiation of mouse embryonic stem cells (ESCs) is regulated by different Cbx-associated PRC1 complexes with unique functions. Maintenance of pluripotency primarily depends on Cbx7, while lineage commitment is orchestrated by Cbx2 and Cbx4. At the molecular level, we have uncovered a Polycomb autoregulatory loop in which Cbx7 represses the expression of prodifferentiation Cbx proteins, thereby maintaining the pluripotent state. We additionally show that the occupancy of Cbx7 on promoters is completely dependent on PRC2 activity but only partially dependent on a functional PRC1 complex. Thus, Cbx proteins confer distinct target selectivity to the PRC1 complex, achieving a balance between the self-renewal and the differentiation of ESCs.
多梳蛋白是胚胎发生过程中细胞命运决定的重要调节因子。在哺乳动物中，已知至少有五种不同的 Cbx 蛋白（Cbx2、Cbx4、Cbx6、Cbx7 和 Cbx8）与核心多梳抑制复合物 1（PRC1）相关联。在这里，我们表明小鼠胚胎干细胞（ESCs）的多能性和分化受不同的 Cbx 相关 PRC1 复合物的调节，具有独特的功能。多能性的维持主要依赖于 Cbx7，而谱系的决定则由 Cbx2 和 Cbx4 协调。在分子水平上，我们发现了一个多梳蛋白的自我调节回路，其中 Cbx7 抑制促分化 Cbx 蛋白的表达，从而维持多能状态。我们还表明，Cbx7 在启动子上的占据完全依赖于 PRC2 活性，但仅部分依赖于功能性 PRC1 复合物。因此，Cbx 蛋白赋予 PRC1 复合物独特的靶标选择性，在 ESCs 的自我更新和分化之间取得平衡。
