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Polycomb Repressive-Deubiquitinase Complex Safeguards Oocyte Epigenome and Female Fertility by Restraining Polycomb Activity

ABSTRACT: Mouse oocytes exhibit a unique chromatin landscape characterized by broad H3K27ac and H3K27me3 domains, demarcating euchromatin and facultative heterochromatin, respectively. However, the mechanisms underlying this non-canonical landscape remain elusive. Here we report BAP1, a core component of the Polycomb Repressive-Deubiquitinase (PR-DUB) complex, as a key negative regulator of Polycomb activity during oogenesis. BAP1 restricts pervasive H2AK119ub1 accumulation in oocytes and protects oocyte-specific broad H3K27ac, particularly within gene-poor regions, from ectopic H3K27me3 deposition. While PR-DUB has been linked to gene repression, in oocytes BAP1 primarily promotes transcription and contributes minimally to Polycomb-mediated silencing. BAP1-dependent transcriptional activation during oogenesis is essential for oocyte developmental competence, maternal-to-zygotic transition, and female fertility. Notably, the aberrant H3K27me3 landscapes established in BAP1-deficient oocytes, but not H3K27ac alterations, persist in preimplantation embryos. The ectopic H3K27me3 domains nonetheless are resolved by early post-implantation stages, and loss of maternal BAP1 does not impair either canonical or non-canonical genomic imprinting. Together, these findings reveal a critical role for PR-DUB in safeguarding the oocyte epigenome by protecting euchromatin from ectopic Polycomb activity, rather than enforcing transcriptional repression.

ORGANISM(S): Mus musculus

PROVIDER: GSE316472 | GEO | 2026/03/19

REPOSITORIES: GEO

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