期刊
ADVANCED SCIENCE
卷 -, 期 -, 页码 -出版社
WILEY
DOI: 10.1002/advs.202303224
关键词
chromatin accessibility; G9a phosphorylation; mitotic progression; Plk1, PPP2CB
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.
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.image
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据