Cross-talk between histone modifications in response to histone deacetylase inhibitors - MLL4 links histone H3 acetylation and histone H3K4 methylation
Cross-talk between histone modifications in response to histone deacetylase inhibitors - MLL4 links histone H3 acetylation and histone H3K4 methylation
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DOI：
10.1074/jbc.m606773200
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发表时间：
2007-02-16
影响因子：
4.8
通讯作者：
Turner, Bryan M.
中科院分区：
文献类型：
--
作者：
Nightingale, Karl P.;Gendreizig, Susanne;Turner, Bryan M.
组蛋白经历多种翻译后修饰，这些修饰在基因激活和沉默中起核心作用。我们已经使用组蛋白修饰特异性抗体来证明两个组蛋白修饰参与基因激活，组蛋白H3乙酰化和H3赖氨酸4甲基化，是功能性连接的。这种相互作用（其中组蛋白H3乙酰化的程度决定了H3 K4甲基化的丰度和“程度”）在对组蛋白脱乙酰酶抑制剂的表观遗传反应中发挥着重要作用。体内敲除实验和体外甲基转移酶测定的组合表明，H3K4甲基化的丰度受两种相反的酶活性的活性调节，甲基转移酶MLL4，其由乙酰化底物刺激，和一种新的且尚未鉴定的H3K4me3去甲基酶。
Histones are subject to a wide variety of post-translational modifications that play a central role in gene activation and silencing. We have used histone modification-specific antibodies to demonstrate that two histone modifications involved in gene activation, histone H3 acetylation and H3 lysine 4 methylation, are functionally linked. This interaction, in which the extent of histone H3 acetylation determines both the abundance and the "degree" of H3K4 methylation, plays a major role in the epigenetic response to histone deacetylase inhibitors. A combination of in vivo knockdown experiments and in vitro methyltransferase assays shows that the abundance of H3K4 methylation is regulated by the activities of two opposing enzyme activities, the methyltransferase MLL4, which is stimulated by acetylated substrates, and a novel and as yet unidentified H3K4me3 demethylase.