2025-08-15 清華大学
A model illustrating the functions of H2A.Z in mouse oocytes
<関連情報>
- https://www.tsinghua.edu.cn/en/info/1245/14427.htm
- https://www.nature.com/articles/s41594-025-01580-y
H2A.Zはメスのマウスの卵母細胞成熟と生殖能力に必須である H2A.Z is essential for oocyte maturation and fertility in female mouse
Qianhua Xu,Chunyi Huang,Jia Ming,Xukun Lu,Ling Liu,Zhenhai Du,Zhen Chen,Jie Na,Guohong Li,Yunlong Xiang,Yu Zhang & Wei Xie
Nature Structural & Molecular Biology Published:13 June 2025
DOI:https://doi.org/10.1038/s41594-025-01580-y
Abstract
Oocyte maturation is essential for both gametogenesis and early development, when large amounts of transcripts are produced without DNA replication. Histone variants, which can be incorporated at cis-regulatory elements in a replication-independent manner, are naturally suited for such regulation. However, their roles during mammalian oocyte maturation remain elusive. Here we show that oocyte-specific depletion of H2A.Z, an evolutionarily conserved histone variant, in female mice results in profound epigenetic and transcriptional alterations, impedes resumption of oocyte meiosis II and causes infertility. Mechanistically, H2A.Z in mouse oocytes is incorporated into chromatin at active promoters and putative enhancers. Interestingly, H2A.Z is depleted from CG-rich silenced promoters, including poised Polycomb target genes, in fully grown oocytes (FGOs), unlike what occurs in growing oocytes, early embryos and mouse embryonic stem cells. In FGOs, the presence of H2A.Z correlates with histone acetylation, except in regions marked by DNA methylation and H3K36me3. Depletion of H2A.Z leads to impaired activities of a subset of promoters and enhancers, correlated with defective gene expression. Consistent with a role in gene activation, H2A.Z in FGOs is widely acetylated at the promoters and enhancers. Together, our findings uncover an essential role of H2A.Z in mammalian oocyte maturation and female fertility.
