Polycomb Repressive Complex 2 (PRC2) plays an essential role in gene repression during development, catalyzing H3 lysine 27 trimethylation (H3K27me3). MTF2 in the PRC2.1 sub-complex, and JARID2 in PRC2.2, are central in core PRC2 recruitment to target genes in mouse embryonic stem cells (mESCs). To investigate how PRC2.1 and PRC2.2 cooperate, we combined Polycomb mutant mESCs with chemical inhibition of binding to H3K27me3. We find that PRC2.1 and PRC2.2 mediate two distinct paths for recruitment, which are mutually reinforced. Whereas PRC2.1 recruitment is mediated by MTF2 binding to DNA, JARID2-containing PRC2.2 recruitment is more dependent on PRC1. Both recruitment axes are supported by core subunit EED binding to H3K27me3, but EED inhibition exhibits a more pronounced effect in Jarid2 null cells. Finally, we show that PRC1 and PRC2 enhance reciprocal binding. Together, these data disentangle the interdependent interactions that are important for PRC2 recruitment.

Polycomb Repressive Complex 2 (PRC2) 在发育过程中的基因抑制中起重要作用，催化 H3 赖氨酸 27 三甲基化 (H3K27me3)。PRC2.1 亚复合体中的 MTF2 和 PRC2.2 中的 JARID2 是核心 PRC2 募集到小鼠胚胎干细胞 (mESCs) 中的靶基因的核心。为了研究PRC2.1和PRC2.2如何合作，我们将Polycomb突变的mESCs与化学抑制结合H3K27me3结合起来。我们发现PRC2.1 和PRC2.2 介导了两条不同的招聘路径，它们相互加强。尽管PRC2.1 招募是由MTF2 与DNA 结合介导的，但含有JARID2 的PRC2.2 招募更依赖PRC1。与 H3K27me3 结合的核心亚基 EED 支持两个募集轴，但 EED 抑制在Jarid2 中表现出更明显的作用空单元格。最后，我们表明PRC1 和PRC2 增强了相互结合。总之，这些数据解开了对PRC2招募很重要的相互依赖的相互作用。