G9a介导的雌激素受体α甲基化将PHF20/MOF组蛋白乙酰转移酶复合物与激素基因表达联系起来。
G9a-mediated methylation of ERα links the PHF20/MOF histone acetyltransferase complex to hormonal gene expression.
作者信息
Zhang Xi, Peng Danni, Xi Yuanxin, Yuan Chao, Sagum Cari A, Klein Brianna J, Tanaka Kaori, Wen Hong, Kutateladze Tatiana G, Li Wei, Bedford Mark T, Shi Xiaobing
机构信息
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
出版信息
Nat Commun. 2016 Mar 10;7:10810. doi: 10.1038/ncomms10810.
The euchromatin histone methyltransferase 2 (also known as G9a) methylates histone H3K9 to repress gene expression, but it also acts as a coactivator for some nuclear receptors. The molecular mechanisms underlying this activation remain elusive. Here we show that G9a functions as a coactivator of the endogenous oestrogen receptor α (ERα) in breast cancer cells in a histone methylation-independent manner. G9a dimethylates ERα at K235 both in vitro and in cells. Dimethylation of ERαK235 is recognized by the Tudor domain of PHF20, which recruits the MOF histone acetyltransferase (HAT) complex to ERα target gene promoters to deposit histone H4K16 acetylation promoting active transcription. Together, our data suggest the molecular mechanism by which G9a functions as an ERα coactivator. Along with the PHF20/MOF complex, G9a links the crosstalk between ERα methylation and histone acetylation that governs the epigenetic regulation of hormonal gene expression.
常染色质组蛋白甲基转移酶2（也称为G9a）使组蛋白H3K9甲基化以抑制基因表达，但它也作为一些核受体的共激活因子发挥作用。这种激活背后的分子机制仍然难以捉摸。在这里，我们表明G9a在乳腺癌细胞中以不依赖组蛋白甲基化的方式作为内源性雌激素受体α（ERα）的共激活因子发挥作用。G9a在体外和细胞内均使ERα的K235位点发生二甲基化。ERα K235位点的二甲基化被PHF20的Tudor结构域识别，该结构域将MOF组蛋白乙酰转移酶（HAT）复合物募集到ERα靶基因启动子上，以沉积组蛋白H4K16乙酰化，促进活性转录。总之，我们的数据揭示了G9a作为ERα共激活因子发挥作用的分子机制。与PHF20/MOF复合物一起，G9a连接了ERα甲基化和组蛋白乙酰化之间的相互作用，这种相互作用控制着激素基因表达的表观遗传调控。
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