日本理研综合医学科学中心Azusa Inoue团队近期取得重要工作进展，他们通过研究H3K27二甲基化动力学，揭示了兼性异染色质在早期小鼠胚胎中的逐步建立过程。相关研究成果2024年10月31日在线发表于《自然—细胞生物学》杂志上。

据介绍，兼性异染色质是由多梳抑制复合物2（PRC2）沉积的H3K27三甲基化（H3K27me3）和PRC1沉积的H2AK119单泛素化（H2AK119ub1）形成的。受精后它是如何新建立的尚不清楚。

为了描述建立动力学，研究人员分析了小鼠植入前胚胎中H3K27二甲基化（H3K27me2）的时间动力学，这代表了PRC2的从头催化作用。H3K27me2新沉积在CpG岛（CGI）、父系X染色体（Xp）和8细胞到桑椹胚过渡期间的假定增强子上，所有这些都遵循H2AK119ub1沉积。研究人员发现JARID2是一种PRC2.2特异性的辅助蛋白，具有H2AK119ub1结合能力，在桑椹胚的CGI和Xp处与SUZ12共定位。JARID2耗竭后，桑椹胚中SUZ12染色质结合和H3K27me2沉积减弱，推测增强子处的H3K27乙酰化增加，随后H3K27me3未能沉积在囊胚中。

总之，这一研究表明，在早期胚胎发育过程中，兼性异染色质是通过PRC2.2驱动的H3K27逐步甲基化沿着预沉积的H2AK119ub1建立的。

附：英文原文

Title: H3K27 dimethylation dynamics reveal stepwise establishment of facultative heterochromatin in early mouse embryos

Author: Matsuwaka, Masahiro, Kumon, Mami, Inoue, Azusa

Issue&Volume: 2024-10-31

Abstract: Facultative heterochromatin is formed by Polycomb repressive complex 2 (PRC2)-deposited H3K27 trimethylation (H3K27me3) and PRC1-deposited H2AK119 mono-ubiquitylation (H2AK119ub1). How it is newly established after fertilization remains unclear. To delineate the establishment kinetics, here we profiled the temporal dynamics of H3K27 dimethylation (H3K27me2), which represents the de novo PRC2 catalysis, in mouse preimplantation embryos. H3K27me2 is newly deposited at CpG islands (CGIs), the paternal X chromosome (Xp) and putative enhancers during the eight-cell-to-morula transition, all of which follow H2AK119ub1 deposition. We found that JARID2, a PRC2.2-specific accessory protein possessing an H2AK119ub1-binding ability, colocalizes with SUZ12 at CGIs and Xp in morula embryos. Upon JARID2 depletion, SUZ12 chromatin binding and H3K27me2 deposition were attenuated and H3K27 acetylation at putative enhancers was increased in morulae and subsequently H3K27me3 failed to be deposited in blastocysts. These data reveal that facultative heterochromatin is established by PRC2.2-driven stepwise H3K27 methylation along pre-deposited H2AK119ub1 during early embryogenesis.

DOI: 10.1038/s41556-024-01553-1

Source: https://www.nature.com/articles/s41556-024-01553-1