H3R42me2a is a histone modification with positive transcriptional effects
H3R42me2a is a histone modification with positive transcriptional effects
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DOI：
10.1073/pnas.1312925110
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发表时间：
2013-09-10
影响因子：
11.1
通讯作者：
Allis, C. David
中科院分区：
文献类型：
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作者：
Casadio, Fabio;Lu, Xiangdong;Allis, C. David
组蛋白翻译后修饰通过允许或阻止效应分子对接间接导致下游效应，或通过改变局部染色质的内在生物物理特性直接导致下游效应。迄今为止，对组蛋白非结构化尾部结构域之外的翻译后修饰的研究还很少。核心残基，特别是 H3 和 H4 中的精氨酸，介导组蛋白八聚体和 DNA 之间形成核小体颗粒的关键相互作用。使用质谱分析，我们发现这些核心残基之一，组蛋白 H3 的精氨酸 42 (H3R42)，在哺乳动物细胞中被甲基转移酶共激活剂精氨酸甲基转移酶 1 (CARM1) 和蛋白质精氨酸甲基转移酶 6 (PRMT6) 在体外和体内二甲基化，并且我们证明 H3R42 的甲基化刺激 从染色质模板进行体外转录。因此，H3R42 是一个新的“非尾”组蛋白甲基化位点，对转录具有积极作用。我们认为 DNA 界面上基本组蛋白残基的甲基化可能会破坏组蛋白：DNA 相互作用，从而影响下游过程，尤其是转录。
Histone posttranslational modification leads to downstream effects indirectly by allowing or preventing docking of effector molecules, or directly by changing the intrinsic biophysical properties of local chromatin. To date, little has been done to study posttranslational modifications that lie outside of the unstructured tail domains of histones. Core residues, and in particular arginines in H3 and H4, mediate key interactions between the histone octamer and DNA in forming the nucleosomal particle. Using mass spectrometry, we find that one of these core residues, arginine 42 of histone H3 (H3R42), is dimethylated in mammalian cells by the methyltransferases coactivator arginine methyltransferase 1 (CARM1) and protein arginine methyltransferase 6 (PRMT6) in vitro and in vivo, and we demonstrate that methylation of H3R42 stimulates transcription in vitro from chromatinized templates. Thus, H3R42 is a new, "nontail" histone methylation site with positive effects on transcription. We propose that methylation of basic histone residues at the DNA interface may disrupt histone: DNA interactions, with effects on downstream processes, notably transcription.