期刊
NATURE GENETICS
卷 53, 期 4, 页码 539-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41588-021-00820-3
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) Leading Initiative for Excellent Young Researchers Grant
- Japan Society for the Promotion of Science (JSPS) [18H02359, 16H02622, 19H05754, 19H05745, 19K17971, 20J21541]
- Japan Agency for Medical Research and Development (PRIME) [JP18gm6110012]
- AMED-CREST [JP18gm0510016]
- Uehara Memorial Foundation
- RIKEN
- All-RIKEN 'Epigenome Manipulation Project'
- Kazusa DNA Research Institute
- Grants-in-Aid for Scientific Research [20J21541, 19H05745, 19H05754, 19K17971, 18H02359] Funding Source: KAKEN
The study reveals the 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. 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.
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