Histone H1-mediated epigenetic regulation controls germline stem cell self-renewal by modulating H4K16 acetylation.
Histone H1-mediated epigenetic regulation controls germline stem cell self-renewal by modulating H4K16 acetylation.
复制标题
组蛋白 H1 介导的表观遗传调控通过调节 H4K16 乙酰化来控制生殖干细胞的自我更新
DOI：
10.1038/ncomms9856
复制
发表时间：
2015-11-19
影响因子：
16.6
通讯作者：
Ni JQ
中科院分区：
文献类型：
--
作者：
Sun J;Wei HM;Xu J;Chang JF;Yang Z;Ren X;Lv WW;Liu LP;Pan LX;Wang X;Qiao HH;Zhu B;Ji JY;Yan D;Xie T;Sun FL;Ni JQ
表观遗传学在控制干细胞自我更新和分化中起着至关重要的作用。组蛋白H1是最关键的染色质调节因子之一，但其在成体干细胞调节中的作用尚不清楚。在这里，我们报道了H1在果蝇生殖系干细胞（GSCs）的调控中是内在必需的。GSC中H1的缺失通过激活关键的GSC分化因子导致其过早分化。有趣的是，乙酰化的H4赖氨酸16 （H4K16ac）在h1缺失的GSCs中选择性地增加。此外，mox的过表达会导致H1在染色质上的关联。相反，敲除的显著挽救GSC损失表型。综上所述，这些结果表明H1通过拮抗MOF功能内在地促进GSC自我更新。由于H1和H4K16乙酰化在果蝇和人类之间高度保守，本研究的发现可能适用于其他系统的干细胞。
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 theDrosophilaovary. The loss of H1 from GSCs causes their premature differentiation through activation of the key GSC differentiation factorbam. Interestingly, the acetylated H4 lysine 16 (H4K16ac) is selectively augmented in the H1-depleted GSCs. Furthermore, overexpression ofmofreduces H1 association on chromatin. In contrast, the knocking down ofmofsignificantly 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.