Histone H1-mediated epigenetic regulation controls germline stem cell self-renewal by modulating H4K16 acetylation

组蛋白 H1 介导的表观遗传调控通过调节 H4K16 乙酰化来控制生殖系干细胞自我更新

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作者:Jin Sun, Hui-Min Wei, Jiang Xu, Jian-Feng Chang, Zhihao Yang, Xingjie Ren, Wen-Wen Lv, Lu-Ping Liu, Li-Xia Pan, Xia Wang, Huan-Huan Qiao, Bing Zhu, Jun-Yuan Ji, Dong Yan, Ting Xie, Fang-Lin Sun, Jian-Quan Ni

Abstract

Epigenetics plays critical roles in controlling stem cell self-renewal and differentiation. Histone H1 is one of the most critical chromatin regulators, but its role in adult stem cell regulation remains unclear. Here we report that H1 is intrinsically required in the regulation of germline stem cells (GSCs) in the Drosophila ovary. The loss of H1 from GSCs causes their premature differentiation through activation of the key GSC differentiation factor bam. Interestingly, the acetylated H4 lysine 16 (H4K16ac) is selectively augmented in the H1-depleted GSCs. Furthermore, overexpression of mof reduces H1 association on chromatin. In contrast, the knocking down of mof significantly rescues the GSC loss phenotype. Taken together, these results suggest that H1 functions intrinsically to promote GSC self-renewal by antagonizing MOF function. Since H1 and H4K16 acetylation are highly conserved from fly to human, the findings from this study might be applicable to stem cells in other systems.

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