Matsuwaka Masahiro, Kumon Mami, Inoue Azusa
Laboratory for Epigenome Inheritance, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Tokyo Metropolitan University, Hachioji, Japan.
Nat Cell Biol. 2025 Jan;27(1):28-38. doi: 10.1038/s41556-024-01553-1. Epub 2024 Oct 31.
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.
兼性异染色质由多梳抑制复合物2（PRC2）介导的H3K27三甲基化（H3K27me3）和PRC1介导的H2AK119单泛素化（H2AK119ub1）形成。受精后它是如何重新建立的仍不清楚。为了描绘其建立动力学，我们在此分析了小鼠植入前胚胎中代表从头PRC2催化作用的H3K27二甲基化（H3K27me2）的时间动态变化。H3K27me2在八细胞向桑葚胚转变过程中于CpG岛、父本X染色体（Xp）和假定的增强子上新沉积，所有这些都发生在H2AK119ub1沉积之后。我们发现JARID2，一种具有H2AK119ub1结合能力的PRC2.2特异性辅助蛋白，在桑葚胚胚胎的CpG岛和Xp处与SUZ12共定位。JARID2缺失后，桑葚胚中SUZ12与染色质的结合及H3K27me2沉积减弱，假定增强子处的H3K27乙酰化增加，随后囊胚中H3K27me３未能沉积。这些数据表明，在早期胚胎发育过程中，兼性异染色质是由PRC2.2驱动的沿着预先沉积的H2AK119ub1逐步进行的H3K27甲基化建立的。
