The transcription factor FOXL2 is required in ovarian somatic cells for female fertility. Differential timing of Foxl2 deletion, in embryonic versus adult mouse ovary, leads to distinctive outcomes, suggesting different roles across development. Here, we comprehensively investigated FOXL2’s role through a multi-omics approach to characterize gene expression dynamics and chromatin accessibility changes, coupled with genome-wide identification of FOXL2 targets and on-chromatin interacting partners in somatic cells across ovarian development. We found that FOXL2 regulates more targets postnatally, through interaction with factors regulating primordial follicle formation and steroidogenesis. Deletion of one interactor, ubiquitin-specific protease 7 (Usp7), results in impairment of somatic cell differentiation, germ cell nest breakdown, and ovarian development, leading to sterility. Our datasets constitute a comprehensive resource for exploration of the molecular mechanisms of ovarian development and causes of female infertility.

中文翻译：

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FOXL2与不同结合伙伴的相互作用调节卵巢发育的动态

卵巢体细胞需要转录因子 FOXL2 来维持女性生育能力。胚胎和成年小鼠卵巢中Foxl2缺失的时间不同，会导致不同的结果，表明在整个发育过程中发挥不同的作用。在这里，我们通过多组学方法全面研究了 FOXL2 的作用，以表征基因表达动态和染色质可及性变化，再加上整个卵巢发育过程中体细胞中 FOXL2 靶标和染色质上相互作用伙伴的全基因组鉴定。我们发现 FOXL2 通过与调节原始卵泡形成和类固醇生成的因子相互作用，在出生后调节更多靶点。删除一种相互作用因子，即泛素特异性蛋白酶 7 ( Usp7 )，会导致体细胞分化、生殖细胞巢破坏和卵巢发育受损，从而导致不育。我们的数据集构成了探索卵巢发育的分子机制和女性不孕原因的综合资源。