Fosl2 facilitates chromatin accessibility to determine developmental events during follicular maturation.

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-10-08 DOI:10.1038/s41467-025-64009-6

Hongyong Zhang,Zechen Li,Yanmei Zhu,Wencong Lyu,Wenlu Wei,Haochen Wang,Shuangjie Tian,Wei Yue,Jiajing Zhong,Qing-Yuan Sun,Yiting Guan

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引用次数: 0

Abstract

Granulosa cells (GCs) are the most dynamically responsive cell lineage to encourage continuous folliculogenesis; however, developmental dynamics and interplay with downstream transcription circuitry remain unclear. Here, we unravel the redistribution of genome-wide chromatin areas that drive broad developmental-related transcriptomic alterations during follicular maturation in murine and porcine GCs. Distinct GC-activated accessibility regions (GAAs) at the ovulatory phase are responsible for augmenting flanking GC-involved developmental gene (GDG) expression, which are essential for transcriptional responses to developmental cues. Mechanistically, the transcription factor Fosl2 is strongly recruited to GAAs, facilitating chromatin accessibility state transition. Elevated GAA signals driven by Fosl2 loading induce a significant upregulation of adjacent GDG expression. Additionally, GC-specific Fosl2 deletion in mice perturbs GC cellularity, leading to subfertility related to reproductive aging. Together, we highlight a dynamic chromatin accessibility landscape during follicular maturation, revealing the indispensable Fosl2 function not only controls transcriptional activation via a reconfigured chromatin state, but also orchestrates intricate signaling pathways that are fundamental for ovulation and reproduction.

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Fosl2促进染色质可及性，以确定卵泡成熟过程中的发育事件。

颗粒细胞（GCs）是最动态响应的细胞谱系，以促进卵泡的持续发生；然而，发育动力学和与下游转录电路的相互作用仍不清楚。在这里，我们揭示了全基因组染色质区域的重新分布，该区域在小鼠和猪GCs的卵泡成熟过程中驱动广泛的发育相关转录组改变。排卵期不同的gc激活可及性区域（GAAs）负责增加侧翼gc相关发育基因（GDG）的表达，这对于发育线索的转录反应至关重要。从机制上讲，转录因子Fosl2被GAAs强烈募集，促进染色质可及性状态的转变。由Fosl2负载驱动的GAA信号升高诱导邻近GDG表达显著上调。此外，小鼠GC特异性的Fosl2缺失会扰乱GC细胞结构，导致与生殖衰老相关的低生育能力。总之，我们强调了卵泡成熟过程中动态染色质可及性景观，揭示了不可或缺的Fosl2功能不仅通过染色质重新配置状态控制转录激活，而且还协调了复杂的信号通路，这些信号通路是排卵和生殖的基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.