Polycomb group proteins (PcGs) maintain transcriptional repression to preserve cellular identity in two distinct repressive complexes, PRC1 and PRC2, that modify histones by depositing H2AK119ub1 and H3K27me3, respectively. PRC1 and PRC2 exist in different variants and show a complex regulatory cross-talk. However, the contribution that H2AK119ub1 plays in mediating PcG repressive functions remains largely controversial. Using a fully catalytic inactive RING1B mutant, we demonstrated that H2AK119ub1 deposition is essential to maintain PcG-target gene repression in embryonic stem cells (ESCs). Loss of H2AK119ub1 induced a rapid displacement of PRC2 activity and a loss of H3K27me3 deposition. This preferentially affected PRC2.2 variant with respect to PRC2.1, destabilizing canonical PRC1 activity. Finally, we found that variant PRC1 forms can sense H2AK119ub1 deposition, which contributes to their stabilization specifically at sites where this modification is highly enriched. Overall, our data place H2AK119ub1 deposition as a central hub that mounts PcG repressive machineries to preserve cell transcriptional identity.

中文翻译：

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组蛋白H2AK119单泛素化对于多梳介导的转录抑制是必不可少的。

聚梳组蛋白（PcGs）维持转录阻遏作用，以保留两个不同的阻抑复合物PRC1和PRC2中的细胞身份，它们分别通过沉积H2AK119ub1和H3K27me3来修饰组蛋白。PRC1和PRC2存在不同的变体，并且显示出复杂的调节串扰。但是，H2AK119ub1在介导PcG抑制功能​​中的作用仍存在很大争议。使用完全催化的无活性RING1B突变体，我们证明了H2AK119ub1沉积对于维持胚胎干细胞（ESC）中的PcG靶基因阻遏至关重要。H2AK119ub1的丢失导致PRC2活性的快速替换和H3K27me3沉积的丢失。相对于PRC2.1，这优先影响了PRC2.2变体，从而使规范的PRC1活性不稳定。最后，我们发现变异的PRC1形式可以感知H2AK119ub1的沉积，这特别有助于在这种修饰高度富集的位点稳定它们。总体而言，我们的数据将H2AK119ub1沉积物作为安装PcG抑制机制以保持细胞转录身份的中心枢纽。