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） 沉积的 H3K27 三甲基化 （H3K27me3） 和 PRC1 沉积H2AK119单泛素化 （H2AK119ub1） 形成。受精后它是如何新建立的尚不清楚。为了描述建立动力学，我们在这里描述了小鼠植入前胚胎中 H3K27 二甲基化 （H3K27me2） 的时间动力学，它代表了从头 PRC2 催化。H3K27me2 在 8 个细胞到桑椹的转变过程中新沉积在 CpG 岛 （CGI）、父系 X 染色体 （Xp） 和推定的增强子上，所有这些都遵循 H2AK119ub1 沉积。我们发现 JARID2 是一种具有 H2AK119ub1 结合能力的 PRC2.2 特异性辅助蛋白，在桑椹胚中与 SUZ12 在 CGI 和 Xp 处共定位。在 JARID2 耗竭后，SUZ12 染色质结合和 H3K27me2 沉积减弱，桑椹中推定增强子的 H3K27 乙酰化增加，随后 H3K27me3 未能沉积在囊胚中。这些数据表明，在早期胚胎发生过程中，PRC2.2 驱动的 H3K27 甲基化沿着预先沉积的 H2AK119ub1 逐步建立兼性异染色质。