Physical association and coordinate function of the H3K4 methyltransferase MLL1 and the H4K16 acetyltransferase MOF
Physical association and coordinate function of the H3K4 methyltransferase MLL1 and the H4K16 acetyltransferase MOF
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DOI：
10.1016/j.cell.2005.04.031
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发表时间：
2005-06-17
期刊：
影响因子：
64.5
通讯作者：
Roeder, RG
中科院分区：
文献类型：
--
作者：
Dou, YL;Milne, TA;Roeder, RG
已经从稳定表达表位标记的WDR 5亚基的人细胞系中免疫亲和纯化了含有MILL 1和MOF的稳定复合物。通过相互免疫沉淀、共沉淀和共转染分析证实了MILL 1和MOF之间的稳定相互作用，并将相互作用位点定位于MLL 1 C-末端和MOF锌指结构域。纯化的复合物具有稳健的MILL 1介导的组蛋白甲基转移酶活性，其可以影响H3 K4的单-、二-和三甲基化，以及特异于H4 K16的MOF介导的组蛋白乙酰转移酶活性。重要的是，这两种活性都是体外染色质模板和体内内源性MLL 1靶基因Hox α 9的最佳转录激活所必需的。这些结果表明，联合MILLI 1和MOF招募和靶向甲基化和乙酰化的激活剂为基础的机制，并提供了H3 K4甲基化和H4 K16乙酰化在活性基因上密切相关的分布的分子解释。
A stable complex containing MILL1 and MOF has been immunoaffinity purified from a human cell line that stably expresses an epitope-tagged WDR5 subunit. Stable interactions between MILL1 and MOF were confirmed by reciprocal immunoprecipitation, cosedimentation, and cotransfection analyses, and interaction sites were mapped to MLL1 C-terminal and MOF zinc finger domains. The purified complex has a robust MILL1-mediated histone methyltransferase activity that can effect mono-, di-, and trimethylation of H3 K4 and a MOF-mediated histone acetyltransferase activity that is specific for H4 K16. Importantly, both activities are required for optimal transcription activation on a chromatin template in vitro and on an endogenous MLL1 target gene, Hox a9, in vivo. These results indicate an activator-based mechanism for joint MILLI1 and MOF recruitment and targeted methylation and acetylation and provide a molecular explanation for the closely correlated distribution of H3 K4 methylation and H4 K16 acetylation on active genes.