H2AK119ub1 guides maternal inheritance and zygotic deposition of H3K27me3 in mouse embryos
H2AK119ub1 guides maternal inheritance and zygotic deposition of H3K27me3 in mouse embryos
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DOI：
10.1038/s41588-021-00820-3
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发表时间：
2021-04-05
期刊：
影响因子：
30.8
通讯作者：
Inoue, Azusa
中科院分区：
文献类型：
--
作者：
Mei, Hailiang;Kozuka, Chisayo;Inoue, Azusa
在早期小鼠胚胎中，prc1介导的H2AK119ub1沉积先于H3K27me3。变异PRC1的缺失减少H2AK119ub1，导致卵母细胞中H3K27me3的基因选择性缺失，这是由胚胎遗传的。亲本表观基因组是在配子体发生过程中建立的。虽然它们在受精后大部分被重置，但小鼠卵母细胞遗传了Polycomb抑制复合体2 （PRC2）介导的赖氨酸27-三甲基化组蛋白H3 （H3K27me3）的广泛结构域。母体H3K27me3是如何被胚胎建立和遗传的仍然是一个谜。在这里，我们发现prc1介导的赖氨酸119-单泛素化组蛋白H2A （H2AK119ub1）的形成赋予母体可遗传的H3K27me3。H2AK119ub1动态的时间分析显示，在卵母细胞生长过程中，H2AK119ub1与H3K27me3一起建立了非典型的宽结构域。从双细胞阶段开始，H2AK119ub1逐渐沉积在典型的Polycomb靶标上，并先于H3K27me3。通过减少Polycomb group ring finger 1 （PCGF1）和pcgf6（变体PRC1 （vPRC1）的必要成分）减少H2AK119ub1，导致卵母细胞中一部分基因的H3K27me3丢失。基因选择性H3K27me3缺陷是胚胎不可逆遗传的，导致母体H3K27me3依赖性印记缺失、胚胎亚致死和足月胎盘增大。总的来说，我们的研究揭示了H2AK119ub1在母体到合子过渡时对H3K27me3的先前动力学，并确定了pcgg1 /6- vprc1在母体表观遗传中起重要作用。
In early mouse embryos, PRC1-mediated H2AK119ub1 deposition precedes H3K27me3. Deficiency in variant PRC1 reduces H2AK119ub1 and leads to gene-selective loss of H3K27me3 in oocytes, which is inherited by embryos.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.