Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins
Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins
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DOI：
10.1038/35065132
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发表时间：
2001-03-01
期刊：
影响因子：
64.8
通讯作者：
Jenuwein, T
中科院分区：
文献类型：
--
作者：
Lachner, M;O'Carroll, N;Jenuwein, T
组蛋白氨基末端的不同修饰，如乙酰化，磷酸化和甲基化，已被提出为基于染色质的调节机制的基础（1，2），调节遗传信息的可及性。除了促进基因活性的组蛋白修饰外，如果细胞和发育程序要不受干扰地进行，限制不适当的基因表达也具有类似的重要性（3，4）。在这里，我们发现哺乳动物甲基转移酶选择性甲基化组蛋白H3赖氨酸9（Suv 39 h HMTases）（5）产生一个结合位点的HP 1蛋白-一个家庭的异染色质衔接分子（6，7）涉及基因沉默和超核小体染色质结构。HP 1对甲基化组蛋白H3肽的高亲和力体外识别需要功能性染色体结构域;因此，HP 1染色体结构域是组蛋白H3的赖氨酸9上的甲基表位的特异性相互作用基序。在体内，HP 1蛋白的异染色质缔合在Suv 39 h双无效原代小鼠成纤维细胞中丢失，但在重新引入催化活性的SUV 39 H1 HMT酶后恢复。我们的数据定义了一种分子机制，通过该机制，SUV 39 H-HP 1甲基化系统可以促进天然染色质中异染色质亚结构域的繁殖。
Distinct modifications of histone amino termini, such as acetylation, phosphorylation and methylation, have been proposed to underlie a chromatin-based regulatory mechanism(1,2) that modulates the accessibility of genetic information. In addition to histone modifications that facilitate gene activity, it is of similar importance to restrict inappropriate gene expression(3,4) if cellular and developmental programmes are to proceed unperturbed. Here we show that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases)(5) generate a binding site for HP1 proteins-a family of heterochromatic adaptor molecules(6,7) implicated in both gene silencing and supra-nucleosomal chromatin structure. High-affinity in vitro recognition of a methylated histone H3 peptide by HP1 requires a functional chromo domain; thus, the HP1 chromo domain is a specific interaction motif for the methyl epitope on lysine 9 of histone H3. In vivo, heterochromatin association of HP1 proteins is lost in Suv39h double-null primary mouse fibroblasts but is restored after the re-introduction of a catalytically active SUV39H1 HMTase. Our data define a molecular mechanism through which the SUV39H-HP1 methylation system can contribute to the propagation of heterochromatic subdomains in native chromatin.