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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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H2AK119ub1 guides maternal inheritance and zygotic deposition of H3K27me3 in mouse embryos
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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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H2AK119ub1 guides maternal inheritance and zygotic deposition of H3K27me3 in mouse embryos
H2AK119ub1 guides maternal inheritance and zygotic deposition of H3K27me3 in mouse embryos
Journal Article

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

2021
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Overview
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. 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.