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. 2025 Oct;32(10):1883-1893.
doi: 10.1038/s41594-025-01573-x. Epub 2025 Jun 13.

H2A.Z reinforces maternal H3K4me3 formation and is essential for meiotic progression in mouse oocytes

Hailiang Mei #  1 , Ryoya Hayashi #  1   2 , Chisayo Kozuka  1 , Mami Kumon  1 , Haruhiko Koseki  3   4 , Azusa Inoue  5   6
Affiliations

H2A.Z reinforces maternal H3K4me3 formation and is essential for meiotic progression in mouse oocytes

Hailiang Mei et al. Nat Struct Mol Biol. 2025 Oct.

Abstract

Mammalian oocytes establish a unique landscape of histone modifications, some of which are inherited by early embryos. How histone variants shape the maternal histone landscape remains unknown. Here we map histone H2A variants in mouse fully grown oocytes (FGOs) and find that H2A.Z forms broad domains across intergenic regions, along non-canonical H3K4me3 (ncH3K4me3). During oocyte growth, H2A.Z progressively transitions from an active promoter-rich, canonical distribution to a non-canonical broad distribution (ncH2A.Z). Depletion of H2A.Z in oocytes partially impairs ncH3K4me3 formation and causes severe defects in meiotic progression, which resemble Mll2-knockout oocytes. Conversely, depletion of ncH3K4me3 by Mll2 knockout also causes a reduction of ncH2A.Z in FGOs. Thus, our study suggests that ncH2A.Z and ncH3K4me3 reinforce each other to form functional oocytes.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

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