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bioRxiv · 10.64898/2026.07.29.741030

NFYA regulates spermatogenesis through multifaceted chromatin interactions

Zhang, Y.·Wang, B.·Jiang, S.·Yang, Q.
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Abstract

During spermatogenesis, germ cells undergo extensive chromatin remodeling to promote highly diverse and stage-specific transcriptional programs that drive differentiation, meiosis, and spermiogenesis. However, conventional loss-of-function approaches do not allow systematic interrogation of gene function across spermatogenesis in vivo. Here, we introduce a protein-degron strategy coupled with intra-seminiferous tubule injection (dTAG-IS) to enable rapid, simultaneous, and stage-resolved functional investigation of NFYA during spermatogenesis. Acute NFYA-depletion induces apoptosis in differentiating spermatogonia (diff-Spg), pachytene spermatocytes (pSpc), and round spermatids (rStd), revealing an essential requirement across spermatogenesis. Mechanistically, NFYA exhibits stage-specific chromatin-binding patterns and directly regulates distinct transcriptional programs, including cell cycle progression and histone assembly in diff-Spg; chromosome organization and DNA damage response in pSpc; and antioxidative stress programs in rStd. Together, our study underscores dTAG-IS as a versatile strategy for in vivo loss-of-function studies during spermatogenesis and establishes NFYA as a multifaceted regulator that drives stage-specific transcriptional programs to ensure spermatogenesis progression.

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Zhang, Y., Wang, B., Jiang, S., Yang, Q.. 2026-07-30. NFYA regulates spermatogenesis through multifaceted chromatin interactions. https://doi.org/10.64898/2026.07.29.741030

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