Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, the Netherlands.
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, the Netherlands.
Stem Cell Reports. 2020 Dec 8;15(6):1287-1300. doi: 10.1016/j.stemcr.2020.07.007. Epub 2020 Aug 6.
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.
多梳抑制复合物 2（PRC2）在发育过程中的基因抑制中发挥着重要作用，催化 H3 赖氨酸 27 三甲基化（H3K27me3）。PRC2.1 亚复合物中的 MTF2 和 PRC2.2 中的 JARID2 是 PRC2 核心募集到小鼠胚胎干细胞（mESC）靶基因的关键。为了研究 PRC2.1 和 PRC2.2 如何合作，我们将 Polycomb 突变 mESC 与化学抑制结合到 H3K27me3 结合。我们发现 PRC2.1 和 PRC2.2 介导两种不同的募集途径，这两种途径是相互加强的。虽然 PRC2.1 的募集是通过 MTF2 与 DNA 的结合介导的，但含有 JARID2 的 PRC2.2 的募集更依赖于 PRC1。这两个募集轴都得到了核心亚基 EED 与 H3K27me3 结合的支持，但 EED 抑制在 Jarid2 缺失细胞中表现出更明显的效果。最后，我们表明 PRC1 和 PRC2 增强了相互结合。总之，这些数据阐明了 PRC2 募集中相互依赖的相互作用。
