Regulation of Methyllysine Readers through Phosphorylation.
Regulation of Methyllysine Readers through Phosphorylation.
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DOI：
10.1021/acschembio.5b00802
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发表时间：
2016-03-18
影响因子：
4
通讯作者：
Kutateladze TG
中科院分区：
文献类型：
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作者：
Andrews FH;Gatchalian J;Krajewski K;Strahl BD;Kutateladze TG
组蛋白的甲基赖氨酸翻译后修饰 (PTM) 为进化上保守的读取结构域创建结合位点，将核宿主蛋白和染色质修饰复合物连接到特定的基因组区域。在这些事件的背景下，相邻的组蛋白 PTM 能够改变读取器对其目标标记的结合活性。这提供了一种 PTM 的“组合读出”机制，可以增强、减少或消除读数器与染色质的关联。在本视角中，我们重点关注最近的研究，描述动态磷酸丝氨酸/苏氨酸/酪氨酸标记对甲基赖氨酸读数器与组蛋白相互作用的影响，总结磷酸/甲基读数的机制方面，并强调这些 PTM 之间串扰的重要性。我们还证明，除了抑制结合并充当真正的开关、促进甲基赖氨酸阅读器与染色质解离之外，磷酸/甲基组合还可以以协作方式共同作用，从而添加可在这些双组蛋白 PTM 中编码的新层监管信息。
Methyllysine post-translational modifications (PTMs) of histones create binding sites for evolutionarily conserved reader domains that link nuclear host proteins and chromatin-modifying complexes to specific genomic regions. In the context of these events, adjacent histone PTMs are capable of altering the binding activity of readers toward their target marks. This provides a mechanism of “combinatorial readout” of PTMs that can enhance, decrease, or eliminate the association of readers with chromatin. In this Perspective, we focus on recent studies describing the impact of dynamic phospho-serine/threonine/tyrosine marks on the interaction of methyllysine readers with histones, summarize mechanistic aspects of the phospho/methyl readout, and highlight the significance of crosstalk between these PTMs. We also demonstrate that in addition to inhibiting binding and serving as a true switch, promoting dissociation of the methyllysine readers from chromatin, the phospho/methyl combination can act together in a cooperative manner—thus adding a new layer of regulatory information that can be encoded in these dual histone PTMs.