Polycomb subunit Pcgf2 mediates ovulation and fertility through transcriptional regulation progesterone receptor.
Polycomb subunit Pcgf2 mediates ovulation and fertility through transcriptional regulation progesterone receptor.
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Polycomb亚基Pcgf2通过转录调节黄体酮受体介导排卵和生育能力
DOI：
10.3389/fcell.2022.1010601
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
卵泡是支持卵母细胞发育的基本结构，为后代提供成熟的卵母细胞。这一过程需要颗粒细胞（GCs）对周期中期激素的激增做出反应，通过一系列基因转录表达的变化导致GCs增殖和分化。表观遗传介质，多梳抑制复合物1（PRC1）已被报道在胎儿卵巢发育的功能。然而，其与卵泡发生和排卵的功能相关性仍然未知。在这项研究中，我们证明了GC选择性消耗PRC1的关键成分PCGF2，导致卵泡丢失，排卵缺陷和发情周期延长，导致雌性小鼠生育力低下。PCGF2在生长卵泡的GC中表达，并在人绒毛膜促性腺激素（hCG）刺激后增加。PCGF2与排卵关键基因孕酮受体（Pgr）的启动子结合，通过靶向hCG激增后H2AK119ub1的表观遗传修饰上调Pgr的表达。同时，Pgr下游基因的表达也明显下降，导致GC特异性Pcgf 2基因敲除小鼠卵泡破裂失败，卵母细胞滞留在黄体内。总之，我们的研究确定PCGF2通过调节激素受体表达对卵泡发生和排卵至关重要。
Ovarian follicles are the fundamental structure to support oocyte development, which provides mature oocytes for offspring. This process requires granulosa cells (GCs) to respond to the midcycle surge of hormones, leading to GC proliferation and differentiation by a series of genes’ transcriptional expression changes. Epigenetic mediator, Polycomb Repressive Complex 1 (PRC1) has been reported to function in fetal ovarian development. However, its functional relevance to folliculogenesis and ovulation remains unknown. In this study, we demonstrated that GC-selective depletion of PCGF2, a key component of PRC1, led to the loss of follicles, ovulation defects, and a lengthened estrus cycle, resulting in subfertility in female mice. The expression of PCGF2 is in the GCs of growing follicles and increases after human chorionic gonadotropin (hCG) stimulation. PCGF2 bound to the promoter of the key ovulation gene progesterone receptor (Pgr) and upregulated the expression of Pgr by targeting the epigenetic modification of H2AK119ub1 after hCG surge. Consistently, the expression of downstream genes of Pgr also sharply decreased, which resulted in the follicular rupture failed and oocyte entrapped in corpus luteum in GC-specific Pcgf2 knockout mice. Together, our study identified that PCGF2 is essential for folliculogenesis and ovulation via modulating hormone receptor expression.
影响因子：
3.5
作者：
Baumann C;De La Fuente R
通讯作者：
De La Fuente R