Fosl2 facilitates chromatin accessibility to determine developmental events during follicular maturation

Hongyong Zhang (), Zechen Li, Yanmei Zhu, Wencong Lyu, Wenlu Wei, Haochen Wang, Shuangjie Tian, Wei Yue, Jiajing Zhong, Qing-Yuan Sun and Yiting Guan ()
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Hongyong Zhang: Guangdong Medical University
Zechen Li: Guangdong Medical University
Yanmei Zhu: Guangdong Medical University
Wencong Lyu: Peking University
Wenlu Wei: Guangdong Medical University
Haochen Wang: Peking University
Shuangjie Tian: Chinese Academy of Sciences
Wei Yue: Shenyang Normal University
Jiajing Zhong: Guangdong Medical University
Qing-Yuan Sun: Guangdong Second Provincial General Hospital
Yiting Guan: Guangdong Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-64009-6

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