Dynamic Phosphorylation of G9a Regulates its Repressive Activity on Chromatin Accessibility and Mitotic Progression.
Dynamic Phosphorylation of G9a Regulates its Repressive Activity on Chromatin Accessibility and Mitotic Progression.
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DOI：
10.1002/advs.202303224
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发表时间：
2023-10
期刊：
影响因子：
15.1
通讯作者：
Du, Hai-Ning
中科院分区：
文献类型：
--
作者：
Geng, Qizhi;Kong, Yue-Yu;Li, Weizhe;Zhang, Jianhao;Ma, Haoli;Zhang, Yuhang;Da, Lin-Tai;Zhao, Yan;Du, Hai-Ning
组蛋白H3的Ser 10磷酸化（H3 S10 p），与邻近的Lys 9甲基化（H3 K9 me）一起，被认为是调节有丝分裂染色质结构的“磷酸甲基开关”。尽管对H3 S10磷酸化的作用有了广泛的了解，但对H3 K9 me 2在有丝分裂期间如何动态调节知之甚少。在此，确定Plk 1激酶在有丝分裂早期在Thr 1045（pT 1045）处磷酸化H3 K9 me 1/2甲基转移酶G9 a/EHMT 2，这减弱了其对H3 K9 me 2的催化活性。携带G9 a的Thr 1045磷酸模拟突变体（T1045 E）的细胞显示降低的H3 K9 me 2水平、增加的染色质可及性和延迟的有丝分裂进展。相比之下，在有丝分裂晚期通过蛋白磷酸酶PPP 2CB使pT 1045去磷酸化，重新激活G9 a活性并上调H3 K9 me 2水平，与H3 S10 p水平降低相关。因此，这些结果提供了对“磷酸甲基开关”的本质的机制解释，并强调了Plk 1和PPP 2CB介导的G9 a活性在染色质组织和有丝分裂进程中的动态调节的重要性。“H3 S10 p-H3 K9 me 2开关”对有丝分裂染色质结构很重要。这项研究揭示了在有丝分裂过程中，激酶Plk 1和磷酸酶PPP 2CB动态磷酸化/去磷酸化甲基转移酶G9 a来调节H3 K9 me 2水平、染色质可及性和有丝分裂进程，这突出了串扰在染色质组织和有丝分裂事件中的重要性。
Phosphorylation of Ser10 of histone H3 (H3S10p), together with the adjacent methylation of Lys9 (H3K9me), has been proposed to function as a ‘phospho‐methyl switch’ to regulate mitotic chromatin architecture. Despite of immense understanding of the roles of H3S10 phosphorylation, how H3K9me2 are dynamically regulated during mitosis is poorly understood. Here, it is identified that Plk1 kinase phosphorylates the H3K9me1/2 methyltransferase G9a/EHMT2 at Thr1045 (pT1045) during early mitosis, which attenuates its catalytic activity toward H3K9me2. Cells bearing Thr1045 phosphomimic mutant of G9a (T1045E) show decreased H3K9me2 levels, increased chromatin accessibility, and delayed mitotic progression. By contrast, dephosphorylation of pT1045 during late mitosis by the protein phosphatase PPP2CB reactivates G9a activity and upregulates H3K9me2 levels, correlated with decreased levels of H3S10p. Therefore, the results provide a mechanistic explanation of the essential of a ‘phospho‐methyl switch’ and highlight the importance of Plk1 and PPP2CB‐mediated dynamic regulation of G9a activity in chromatin organization and mitotic progression. ‘H3S10p‐H3K9me2 switch’ is important for mitotic chromatin architecture. This study uncovers that, during mitosis, the kinase Plk1 and the phosphatase PPP2CB dynamically phosphorylates/dephosphorylates the methyltransferase G9a to regulate H3K9me2 levels, chromatin accessibility, and mitotic progression, which highlights the importance of the crosstalk in chromatin organization and mitotic events.
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DOI：
10.1016/j.tig.2015.11.001
发表时间：
2016-01
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Yang Y
影响因子：
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作者：
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Dumontet, Charles
影响因子：
4.6
作者：
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通讯作者：
Johansen, Kristen M.
影响因子：
8.8
作者：
Jiang, Qinghong;Ang, Julie Y. J.;Leung, Danny C. Y.
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