Rb targets histone H3 methylation and HP1 to promoters
Rb targets histone H3 methylation and HP1 to promoters
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DOI：
10.1038/35087620
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发表时间：
2001-08-02
期刊：
影响因子：
64.8
通讯作者：
Kouzarides, T
中科院分区：
文献类型：
--
作者：
Nielsen, SJ;Schneider, R;Kouzarides, T
在真核细胞中，组蛋白甲基化酶SUV 39 H1和甲基赖氨酸结合蛋白HP 1在功能上相互作用，以抑制异染色质位点的转录（1）。组蛋白H3的赖氨酸9被SUV 39 H1甲基化（参考文献2），产生HP 1的染色体结构域的结合位点（参考文献3、4）。在这里，我们表明，SUV 39 H1和HP 1都参与了视网膜母细胞瘤（Rb）蛋白的抑制功能。Rb通过其口袋结构域与SUV 39 H1和HP 1在体内缔合。SUV 39 H1与Rb合作抑制细胞周期蛋白E启动子，并且在因SUV 39而被破坏的成纤维细胞中，细胞周期蛋白E和细胞周期蛋白A2基因的活性特异性升高。染色质免疫沉淀显示Rb对组蛋白H3的直接甲基化是必需的，并且对HP 1与细胞周期蛋白E启动子的结合是必需的。这些结果表明，SUV 39 H1-HP 1复合物不仅参与异染色质沉默，而且还具有Rb和可能的其他共阻遏蛋白对常染色质基因的阻遏作用。
In eukaryotic cells the histone methylase SUV39H1 and the methyl-lysine binding protein HP1 functionally interact to repress transcription at heterochromatic sites(1). Lysine 9 of histone H3 is methylated by SUV39H1 (ref. 2), creating a binding site for the chromo domain of HP1 (refs 3, 4). Here we show that SUV39H1 and HP1 are both involved in the repressive functions of the retinoblastoma (Rb) protein. Rb associates with SUV39H1 and HP1 in vivo by means of its pocket domain. SUV39H1 cooperates with Rb to repress the cyclin E promoter, and in fibroblasts that are disrupted for SUV39, the activity of the cyclin E and cyclin A2 genes are specifically elevated. Chromatin immunoprecipitations show that Rb is necessary to direct methylation of histone H3, and is necessary for binding of HP1 to the cyclin E promoter. These results indicate that the SUV39H1-HP1 complex is not only involved in heterochromatic silencing but also has a role in repression of euchromatic genes by Rb and perhaps other co-repressor proteins.