日本理化研究所Azusa Inoue团队发现，H2AK119ub1指导小鼠胚胎中H3K27me3的母本遗传。该项研究成果于2021年4月5日在线发表在《自然—遗传学》杂志上。

研究人员表示，配子发生过程中建立了亲本的表观基因组。尽管它们在受精后会大量重置，但Polycomb阻抑复合物2（PRC2）介导的组蛋白H3第27位赖氨酸三甲基化（H3K27me3）形成的宽泛分布是从小鼠卵母细胞遗传而来的。胚胎如何建立和继承母体H3K27me3仍然不清楚。

研究人员发现，PRC1介导的组蛋白H2A第119位赖氨酸单泛素化（H2AK119ub1）的形成赋予了可遗传的H3K27me3。H2AK119ub1动态的时间分析表明，在卵母细胞生长过程中，建立了非典型的H2AK119ub1宽泛分布以及H3K27me3。从两细胞阶段开始，H2AK119ub1逐渐积累在典型的Polycomb靶标上，并先于H3K27me3。

通过消除PCGF1和PCGF6（PRC1变体的必须组分）来减少H2AK119ub1，会导致卵母细胞基因的一个亚群出现H3K27me3缺失。基因选择性的H3K27me3缺失是不可逆地由胚胎遗传的，并导致母体H3K27me3依赖的印记丧失、足月胚胎亚致死率和胎盘增大。

总体而言，这项研究揭示了母体向合子转变时H2AK119ub1在H3K27me3之前的动态，并确定PCGF1/6–vPRC1在母体表观遗传中扮演的重要角色。 

附：英文原文

Title: H2AK119ub1 guides maternal inheritance and zygotic deposition of H3K27me3 in mouse embryos

Author: Hailiang Mei, Chisayo Kozuka, Ryoya Hayashi, Mami Kumon, Haruhiko Koseki, Azusa Inoue

Issue&Volume: 2021-04-05

Abstract: Parental epigenomes are established during gametogenesis. While they are largely reset after fertilization, broad domains of Polycomb repressive complex 2 (PRC2)-mediated formation of lysine 27–trimethylated histone H3 (H3K27me3) are inherited from oocytes in mice. How maternal H3K27me3 is established and inherited by embryos remains elusive. Here, we show that PRC1-mediated formation of lysine 119–monoubiquititinated histone H2A (H2AK119ub1) confers maternally heritable H3K27me3. Temporal profiling of H2AK119ub1 dynamics revealed that atypically broad H2AK119ub1 domains are established, along with H3K27me3, during oocyte growth. From the two-cell stage, H2AK119ub1 is progressively deposited at typical Polycomb targets and precedes H3K27me3. Reduction of H2AK119ub1 by depletion of Polycomb group ring finger 1 (PCGF1) and PCGF6—essential components of variant PRC1 (vPRC1)—leads to H3K27me3 loss at a subset of genes in oocytes. The gene-selective H3K27me3 deficiency is irreversibly inherited by embryos, causing loss of maternal H3K27me3-dependent imprinting, embryonic sublethality and placental enlargement at term. Collectively, our study unveils preceding dynamics of H2AK119ub1 over H3K27me3 at the maternal-to-zygotic transition, and identifies PCGF1/6–vPRC1 as an essential player in maternal epigenetic inheritance.

DOI: 10.1038/s41588-021-00820-3

Source: https://www.nature.com/articles/s41588-021-00820-3