De novo methylation of histone H3K23 by the methyltransferases EHMT1/GLP and EHMT2/G9a.
De novo methylation of histone H3K23 by the methyltransferases EHMT1/GLP and EHMT2/G9a.
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DOI：
10.1186/s13072-022-00468-1
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发表时间：
2022-11-21
影响因子：
3.9
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中科院分区：
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组蛋白的表观遗传修饰在调节染色质的允许和抑制状态中起着重要的作用，但是尽管鉴定了许多组蛋白ptm及其感知的作用，但负责产生这些染色质特征的表观遗传作者尚未得到充分的表征。在这里，我们报道了典型的组蛋白H3K9甲基转移酶EHMT1/GLP和EHMT2/G9a能够催化组蛋白H3赖氨酸23 （H3K23）的甲基化。我们的数据表明，虽然这两种酶都可以将H3K23单甲基化和二甲基化，但只有EHMT1/GLP可以将H3K23三甲基化。我们还发现，EHMT1/GLP和/或EHMT2/G9a的药物抑制或基因消融导致哺乳动物细胞中H3K23甲基化降低。综上所述，本研究确定H3K23是EHMT1/GLP和EHMT2/G9a的一个新的直接甲基化靶点，并强调了这些酶对H3K23作为底物的差异活性。在线版本包含补充材料，可在10.1186/s13072-022-00468-1获得。
Epigenetic modifications to histone proteins serve an important role in regulating permissive and repressive chromatin states, but despite the identification of many histone PTMs and their perceived role, the epigenetic writers responsible for generating these chromatin signatures are not fully characterized. Here, we report that the canonical histone H3K9 methyltransferases EHMT1/GLP and EHMT2/G9a are capable of catalyzing methylation of histone H3 lysine 23 (H3K23). Our data show that while both enzymes can mono- and di-methylate H3K23, only EHMT1/GLP can tri-methylate H3K23. We also show that pharmacologic inhibition or genetic ablation of EHMT1/GLP and/or EHMT2/G9a leads to decreased H3K23 methylation in mammalian cells. Taken together, this work identifies H3K23 as a new direct methylation target of EHMT1/GLP and EHMT2/G9a, and highlights the differential activity of these enzymes on H3K23 as a substrate. The online version contains supplementary material available at 10.1186/s13072-022-00468-1.