Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9
Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9
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DOI：
10.1101/gad.1284005
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发表时间：
2005-04-01
影响因子：
10.5
通讯作者：
Shinkai, Y
中科院分区：
文献类型：
--
作者：
Tachibana, M;Ueda, J;Shinkai, Y
组蛋白H3 Lys 9（H3-K9）甲基化是转录沉默的重要表观遗传标记。G9 a是哺乳动物中主要的H3-K9甲基转移酶，靶向常染色质区域，对小鼠胚胎发生至关重要。在哺乳动物中存在一种与G9 a相关的甲基转移酶，称为GLP/Eu-HMTase 1。在这里，我们表明GLP对小鼠常染色质的H3-K9甲基化也很重要。GLP缺陷导致胚胎死亡、H3-K9单甲基化和二甲基化的严重减少、Mage-a基因表达的诱导以及HP 1在胚胎干细胞中的重新定位，所有这些都是G9 a缺陷的表型。此外，我们发现G9 a和GLP在多种细胞类型中形成了化学计量的异聚复合物。生化分析表明，G9 a/GLP复合物的形成依赖于它们的酶促SET结构域。总之，我们的新发现表明，G9 a和GLP在体内协同发挥H3-K9甲基转移酶功能，可能是通过形成高阶异聚复合物。
Histone H3 Lys 9 (H3-K9) methylation is a crucial epigenetic mark for transcriptional silencing. G9a is the major mammalian H3-K9 methyltransferase that targets euchromatic regions and is essential for murine embryogenesis. There is a single G9a-related methyltransferase in mammals, called GLP/Eu-HMTase1. Here we show that GLP is also important for H3-K9 methylation of mouse euchromatin. GLP-deficiency led to embryonic lethality, a severe reduction of H3-K9 mono- and dimethylation, the induction of Mage-a gene expression, and HP1 relocalization in embryonic stem cells, all of which were phenotypes of G9a-deficiency. Furthermore, we show that G9a and GLP formed a stoichiometric heteromeric complex in a wide variety of cell types. Biochemical analyses revealed that formation of the G9a/GLP complex was dependent on their enzymatic SET domains. Taken together, our new findings revealed that G9a and GLP cooperatively exert H3-K9 methyltransferase function in vivo, likely through the formation of higher-order heteromeric complexes.