TY - JOUR
T1 - PRC1-mediated epigenetic programming is required to generate the ovarian reserve
AU - Hu, Mengwen
AU - Yeh, Yu Han
AU - Munakata, Yasuhisa
AU - Abe, Hironori
AU - Sakashita, Akihiko
AU - Maezawa, So
AU - Vidal, Miguel
AU - Koseki, Haruhiko
AU - Hunter, Neil
AU - Schultz, Richard M.
AU - Namekawa, Satoshi H.
N1 - Funding Information:
We thank Azusa Inoue for critical reading of the manuscript; Artem Barski for sharing reagents; M. Azim Surani for sharing Stella-GFP transgenic mice, Wei Xie for sharing the CUT&RUN protocol and the Polycomb targets gene list; Yuki Horisawa-Takada and Kei-Ichiro Ishiguro for discussion of PRC1’s function in gametogenesis. Funding sources: National Institutes of Health grants R01GM122776 and R35GM141085 to S.H.N.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-31759-6
DO - 10.1038/s41467-022-31759-6
M3 - Article
C2 - 35948547
AN - SCOPUS:85135805728
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4510
ER -