摘要
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.
摘要译文
对组蛋白蛋白的表观遗传修饰在调节允许性和抑制性染色质状态中起着重要作用，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并未完全表征。在这里，我们报告说，规范组蛋白H3K9甲基转移酶EHMT1/GLP和EHMT2/G9A能够催化组蛋白H3赖氨酸23（H3K23）的组蛋白H3赖氨酸甲基化（H3K23）。我们的数据表明，虽然这两种酶都可以单甲基酸H3K23和二甲基盐H3K23，但只有EHMT1/GLP可以三甲基盐H3K23。我们还表明，EHMT1/GLP和/或EHMT2/G9A的药理抑制或遗传消融导致哺乳动物细胞中H3K23甲基化降低。综上所述，这项工作将H3K23鉴定为EHMT1/GLP和EHMT2/G9A的新直接甲基化靶标，并突出了这些酶在H3K23作为底物上的差异活性。
Vinson; David A.[1];Stephens; Kimberly E.[1];O’Meally; Robert N.[2];Bhat; Shri[1];Dancy; Blair C. R.[1];Cole; Robert N.[2];Yegnasubramanian; Srinivasan[3];Taverna; Sean D.[1]. De novo methylation of histone H3K23 by the methyltransferases EHMT1/GLP and EHMT2/G9a[J]. Epigenetics & Chromatin, 2022,15(1): 1-13