Histone H3 Threonine Phosphorylation Regulates Asymmetric Histone Inheritance in the Drosophila Male Germline.
Histone H3 Threonine Phosphorylation Regulates Asymmetric Histone Inheritance in the Drosophila Male Germline.
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DOI：
10.1016/j.cell.2015.10.002
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发表时间：
2015-11-05
期刊：
影响因子：
64.5
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Xie J;Wooten M;Tran V;Chen BC;Pozmanter C;Simbolon C;Betzig E;Chen X
一个长期存在的问题是干细胞如何通过多次分裂保持其身份。先前我们报道了果蝇雄性生殖系干细胞（GSC）不对称分裂过程中预先存在的和新合成的组蛋白H3的不对称分布。在这里，我们表明，磷酸化在Three3的H3（H3T3P）区分预先存在的与新合成的H3。将T3转化为不可磷酸化的残基丙氨酸（H3T3A）或磷酸模拟天冬氨酸（H3T3D）会破坏不对称H3遗传。H3T3A或H3T3D在早期生殖系中的特异性表达也导致细胞缺陷，包括GSC损失和生殖系肿瘤。最后，损害H3T3激酶Haspin的活性增强H3T3A，但抑制H3T3D表型。总之，这些研究表明，H3T3P区分富含不同H3库的姐妹染色单体，协调“旧”H3到GSC中的不对称分离，并且H3T3磷酸化的严格调节是雄性生殖系活性所需的。
A long-standing question concerns how stem cells maintain their identity through multiple divisions. Previously we reported that pre-existing and newly synthesized histone H3 are asymmetrically distributed during Drosophila male germline stem cell (GSC) asymmetric division. Here we show that phosphorylation at Threonine 3 of H3 (H3T3P) distinguishes preexisting versus newly synthesized H3. Converting T3 to the unphosphorylatable residue alanine (H3T3A) or to the phosphomimetic aspartate (H3T3D) disrupts asymmetric H3 inheritance. Expression of H3T3A or H3T3D specifically in early-stage germline also leads to cellular defects including GSC loss and germline tumors. Finally, compromising the activity of the H3T3 kinase Haspin enhances the H3T3A but suppresses the H3T3D phenotypes. Together these studies demonstrate that H3T3P distinguishes sister chromatids enriched with distinct pools of H3, coordinating asymmetric segregation of “old” H3 into GSCs, and that a tight regulation of H3T3 phosphorylation is required for male germline activity.