Towards understanding methyllysine readout.
Towards understanding methyllysine readout.
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DOI：
10.1016/j.bbagrm.2014.04.001
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Kutateladze TG
中科院分区：
文献类型：
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作者：
Musselman CA;Khorasanizadeh S;Kutateladze TG
赖氨酸甲基化是在组蛋白和非组蛋白蛋白中发现的最通用的共价翻译后修饰(PTM)。在过去的十年里，已经发现了一些甲基赖氨酸特异的阅读器，并对它们与组蛋白尾巴的相互作用进行了结构和生化表征。最近出现了创新的实验方法，允许在完整的核小体和核小体阵列的背景下研究读者的相互作用。新的研究揭示了组蛋白尾部甲基化之外的各种读者-核小体接触，从而为组蛋白读者与染色质的联系提供了一个更好的模型，并拓宽了我们对这些相互作用的功能含义的理解。本文简要综述了组蛋白赖氨酸甲基化读出的已知机制，总结了最近在探索与甲基化核小体相互作用方面的进展，并讨论了甲基赖氨酸特异读出的小分子抑制剂的最新进展。
Lysine methylation is the most versatile covalent posttranslational modification (PTM) found in histones and non-histone proteins. Over the past decade a number of methyllysine-specific readers have been discovered and their interactions with histone tails have been structurally and biochemically characterized. More recently innovative experimental approaches have emerged that allow for studying reader interactions in the context of the full nucleosome and nucleosomal arrays. New studies reveal various reader-nucleosome contacts outside the methylated histone tail, thus offering a better model for the association of histone readers to chromatin and broadening our understanding of the functional implications of these interactions. In this review we give a brief overview of the known mechanisms of histone lysine methylation readout, summarize progress recently made in exploring interactions with methylated nucleosomes, and discuss the latest advances in the development of small molecule inhibitors of the methyllysine-specific readers.