mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression
mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression
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DOI：
10.1016/j.molcel.2003.08.007
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发表时间：
2003-08-01
期刊：
影响因子：
16
通讯作者：
Zhang, Y
中科院分区：
文献类型：
--
作者：
Wang, HB;An, WJ;Zhang, Y
组蛋白尾部甲基化在染色质结构和功能中起着重要作用。以前，我们报道ESET/SETDB 1是一种组蛋白甲基转移酶（HMTase）。在这里，我们表明，SETDB1紧密相关的人类同源物的mAM，鼠ATFa相关因子。虽然重组ESET可以甲基化组蛋白H3的赖氨酸9（H3-K9），但与ESET/mAM复合物相比，其活性严重受损。mAM通过增加V-max和降低Km来刺激ESET酶活性。重要的是，在体外和体内，mAM促进二甲基H3-K9向三甲基状态的ESET依赖性转化。基于染色质的转录和ChIP分析表明，mAM以SAM依赖性方式增强ESET介导的转录抑制，并且这种抑制与启动子处的H3-K9三甲基化相关。因此，我们的研究确定启动子H3-K9三甲基化是转录抑制的原因，并且mAM/hAM促进通过ESET/SETDBi将H3-K9二甲基转化为三甲基。
Methylation of histone tails plays an important role in chromatin structure and function. Previously, we reported that ESET/SETDB1 is a histone methyltransferase (HMTase). Here, we show that SETDB1 tightly associates with the human homolog of mAM, a murine ATFa-associated factor. Although recombinant ESET can methylate lysine 9 of histone H3 (H3-K9), its activity is severely compromised when compared to that of the ESET/mAM complex. mAM stimulates ESET enzymatic activity by increasing the V-max and decreasing the Km. Importantly, mAM facilitates the ESET-dependent conversion of dimethyl H3-K9 to the trimethyl state both in vitro and in vivo. Chromatin-based transcription and ChIP analyses demonstrate that mAM enhances ESET-mediated transcriptional repression in a SAM-dependent manner, and this repression correlates with H3-K9 trimethylation at the promoter. Thus, our studies establish that promoter H3-K9 trimethylation is the cause of transcriptional repression and that mAM/hAM facilitates conversion of H3-K9 dimethyl to trimethyl by ESET/SETDBi.