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PRC1-mediated epigenetic programming is required to generate the ovarian reserve

Author

Listed:
  • Mengwen Hu

    (University of California, Davis
    Perinatal Institute, Cincinnati Children’s Hospital Medical Center)

  • Yu-Han Yeh

    (University of California, Davis
    Perinatal Institute, Cincinnati Children’s Hospital Medical Center)

  • Yasuhisa Munakata

    (University of California, Davis
    Perinatal Institute, Cincinnati Children’s Hospital Medical Center)

  • Hironori Abe

    (University of California, Davis
    Perinatal Institute, Cincinnati Children’s Hospital Medical Center)

  • Akihiko Sakashita

    (Perinatal Institute, Cincinnati Children’s Hospital Medical Center
    Keio University School of Medicine)

  • So Maezawa

    (Perinatal Institute, Cincinnati Children’s Hospital Medical Center
    Tokyo University of Science)

  • Miguel Vidal

    (Centro de Investigaciones Biológicas Margarita Salas, Department of Cellular and Molecular Biology)

  • Haruhiko Koseki

    (RIKEN Center for Allergy and Immunology)

  • Neil Hunter

    (University of California, Davis
    University of California, Davis)

  • Richard M. Schultz

    (University of Pennsylvania
    University of California, Davis)

  • Satoshi H. Namekawa

    (University of California, Davis
    Perinatal Institute, Cincinnati Children’s Hospital Medical Center)

Abstract

The ovarian reserve defines the female reproductive lifespan, which in humans spans decades due to robust maintenance of meiotic arrest in oocytes residing in primordial follicles. Epigenetic reprogramming, including DNA demethylation, accompanies meiotic entry, but the chromatin changes that underpin the generation and preservation of ovarian reserves are poorly defined. We report that the Polycomb Repressive Complex 1 (PRC1) establishes repressive chromatin states in perinatal mouse oocytes that directly suppress the gene expression program of meiotic prophase-I and thereby enable the transition to dictyate arrest. PRC1 dysfuction causes depletion of the ovarian reserve and leads to premature ovarian failure. Our study demonstrates a fundamental role for PRC1-mediated gene silencing in female reproductive lifespan, and reveals a critical window of epigenetic programming required to establish ovarian reserve.

Suggested Citation

  • Mengwen Hu & Yu-Han Yeh & Yasuhisa Munakata & Hironori Abe & Akihiko Sakashita & So Maezawa & Miguel Vidal & Haruhiko Koseki & Neil Hunter & Richard M. Schultz & Satoshi H. Namekawa, 2022. "PRC1-mediated epigenetic programming is required to generate the ovarian reserve," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31759-6
    DOI: 10.1038/s41467-022-31759-6
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    References listed on IDEAS

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