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

PRC1-mediated epigenetic programming is required to generate the ovarian reserve.
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DOI:
10.1038/s41467-022-31759-6
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发表时间:
2022-08-10
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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卵巢储备决定了女性的生殖寿命,在人类中,由于原始卵泡中卵母细胞减数分裂停滞的稳定维持,生殖寿命长达数十年。表观遗传重编程,包括DNA去甲基化,伴随着减数分裂进入,但染色质的变化,支持卵巢储备的产生和保存是不明确的。我们报告说,Polycomb抑制复合物1(PRC 1)建立抑制性染色质状态在围产期小鼠卵母细胞,直接抑制减数分裂前蛋白酶-I的基因表达程序,从而使过渡到dictyate逮捕。PRC 1功能障碍导致卵巢储备耗竭,导致卵巢早衰。我们的研究证明了PRC 1介导的基因沉默在女性生殖寿命中的基本作用,并揭示了建立卵巢储备所需的表观遗传编程的关键窗口。在人类中,卵巢储备通过卵母细胞的减数分裂停滞维持数十年。在这里,作者表明Polycomb抑制复合物1(PRC 1)介导的表观遗传编程对于卵巢储备的形成以及女性生殖寿命至关重要。
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. In humans, the ovarian reserve is maintained over decades by meiotic arrest of oocytes. Here the authors show that Polycomb Repressive Complex 1 (PRC1)-mediated epigenetic programming is essential for formation of ovarian reserve and thus female reproductive lifespan.
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