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<p>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 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, ectopic H3K27me3 domains established in BAP1-deficient oocytes persist in preimplantation embryos but are resolved after implantation, 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.</p>

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Polycomb repressive-deubiquitinase complex safeguards oocyte epigenome and female fertility by restraining Polycomb activity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月19日

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  • Jinwen Kang,
  • Peiyao Liu,
  • Shoko Ichimura,
  • Lauryn Cook,
  • Mengwen Hu,
  • Satoshi H. Namekawa,
  • Zhiyuan Chen

摘要

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 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, ectopic H3K27me3 domains established in BAP1-deficient oocytes persist in preimplantation embryos but are resolved after implantation, 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.