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Chd1 chromodomain links histone H3 methylation with SAGA- and SUK-dependent acetylation

机译:Chd1染色体域将组蛋白H3甲基化与SAGA和SUK依赖的乙酰化联系起来

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The specific post-translational modifications to histones influence many nuclear processes including gene regulation, DNA repair and replication. Recent studies have identified effector proteins that recognize patterns of histone modification and transduce their function in downstream processes. For example, histone acetyltransferases (HATs) have been shown to participate in many essential cellular processes, particularly those associated with activation of transcription. Yeast SAGA (Spt-Ada-Gcn5 acetyltransferase) and SLIK (SAGA-like) are two highly homologous and conserved multi-subunit HAT complexes, which preferentially acetylate histones H3 and H2B and deubiquitinate histone H2B. Here we identify the chromatin remodelling protein Chdl (chromo-ATPase/helicase-DNA binding domain 1) as a component of SAGA and SLIK. Our findings indicate that one of the two chromodomains of Chd1 specifically interacts with the methylated lysine 4 mark on histone H3 that is associated with transcriptional activity. Furthermore, the SLIK complex shows enhanced acetylation of a methylated substrate and this activity is dependent upon a functional methyl-binding chromodomain, both in vitro and in vivo. Our study identifies the first chromodomain that recognizes methylated histone H3 (Lys 4) and possibly identifies a larger subfamily of chromodomain proteins with similar recognition properties.
机译:对组蛋白的特定翻译后修饰影响许多核过程,包括基因调控,DNA修复和复制。最近的研究已经鉴定出了可以识别组蛋白修饰模式并在下游过程中转导其功能的效应蛋白。例如,组蛋白乙酰转移酶(HATs)已显示出参与许多重要的细胞过程,特别是与转录激活相关的过程。酵母SAGA(Spt-Ada-Gcn5乙酰转移酶)和SLIK(SAGA样)是两个高度同源且保守的多亚基HAT复合物,它们优先乙酰化组蛋白H3和H2B并去泛素化组蛋白H2B。在这里,我们确定染色质重塑蛋白Chdl(chromo-ATPase / helicase-DNA结合域1)作为SAGA和SLIK的组成部分。我们的发现表明,Chd1的两个色域之一与组蛋白H3上与转录活性相关的甲基化赖氨酸4标记特异性相互作用。此外,SLIK复合物显示出甲基化底物的乙酰化增强,并且该活性在体外和体内都取决于功能性的甲基结合色域。我们的研究确定了第一个识别甲基化组蛋白H3(Lys 4)的色域,并可能识别了具有相似识别特性的更大的色域蛋白亚家族。

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