Dynamic Phosphorylation of G9a Regulates its Repressive Activity on Chromatin Accessibility and Mitotic Progression.

Adv Sci (Weinh)

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Hubei Clinical Research Center of Emergency and Resuscitation, Emergency Center of Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, RNA Institute, Wuhan University, Wuhan, 430072, China.

Published: October 2023

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602519PMC
http://dx.doi.org/10.1002/advs.202303224DOI Listing

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