Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1.1 complex, is critical for maintaining primed pluripotency in human embryonic stem cells (ESCs). BCOR depletion leads to the erosion of Polycomb domains at key developmental loci and the initiation of differentiation along endoderm and mesoderm lineages. The C terminus of BCOR regulates the assembly and targeting of the PRC1.1 complex, while the N terminus contributes to BCOR-PRC1.1 repressor function. Our findings advance understanding of Polycomb targeting and repression in ESCs and could apply broadly across developmental systems.

中文翻译：

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非规范的BCOR-PRC1.1复合体抑制人类ESC中的分化程序。

聚梳组蛋白可调节许多干细胞系统中的自我更新和分化。当组装成两个规范复合物PRC1和PRC2时，它们顺序沉积H3K27me3和H2AK119ub组蛋白标记并建立阻抑的染色质，称为多梳结构域。非规范的PRC1复合物保留RING1 / RNF2 E3-泛素连接酶，但具有独特的辅助亚基集。这些非规范复合物如何识别和调节其基因靶点仍然知之甚少。在这里，我们显示BCL6协同阻遏物（BCOR），PRC1.1复合物的成员，对于维持人类胚胎干细胞（ESCs）中的初潜性多能性至关重要。BCOR耗尽导致关键发育位点的Polycomb域被侵蚀，并沿内胚层和中胚层谱系开始分化。BCOR的C末端调节PRC1.1复合物的装配和靶向，而N末端有助于BCOR-PRC1.1阻遏物功能。我们的发现提高了对ESC中Polycomb靶向和抑制的了解，并且可以广泛应用于整个开发系统。