Chemical and biological tools for the preparation of modified histone proteins.
Chemical and biological tools for the preparation of modified histone proteins.
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DOI：
10.1007/128_2015_629
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发表时间：
2015
影响因子：
8.6
通讯作者：
Ottesen JJ
中科院分区：
文献类型：
--
作者：
Howard CJ;Yu RR;Gardner ML;Shimko JC;Ottesen JJ
真核染色质是一个复杂的动态系统，其中DNA双螺旋通过与组蛋白的相互作用而被组织和保护。该系统通过一个大型的动态翻译后修饰（PTM）网络进行调节，以确保正确的基因转录，DNA修复和其他涉及DNA的过程。具有精确表征的修饰位点的均质蛋白样品对于更好地理解修饰的组蛋白的功能是必要的。在这里，我们讨论了一套化学和生物学的工具，已开发的修饰组蛋白的制备，重点是适当的工具选择一个给定的目标。我们从遗传学方法开始，用于创建修饰的组蛋白，包括组蛋白修饰的遗传模拟物的掺入，修饰类似物的化学安装，以及使用扩展的遗传密码来掺入修饰的氨基酸。此外，我们还将介绍化学连接技术，这些技术在生成复杂的修饰组蛋白方面非常宝贵，这些修饰组蛋白与天然组蛋白无法区分。最后，我们将结束与未来的方向在生活系统中的合成染色质的招股说明书。
Eukaryotic chromatin is a complex and dynamic system in which the DNA double helix is organized and protected by interactions with histone proteins. This system is regulated through, a large network of dynamic post-translational modifications (PTMs) exists to ensure proper gene transcription, DNA repair, and other processes involving DNA. Homogenous protein samples with precisely characterized modification sites are necessary to better understand the functions of modified histone proteins. Here, we discuss sets of chemical and biological tools that have been developed for the preparation of modified histones, with a focus on the appropriate choice of tool for a given target. We start with genetic approaches for the creation of modified histones, including the incorporation of genetic mimics of histone modifications, chemical installation of modification analogs, and the use of the expanded genetic code to incorporate modified amino acids. Additionally, we will cover the chemical ligation techniques that have been invaluable in the generation of complex modified histones that are indistinguishable from the natural counterparts. Finally, we will end with a prospectus on future directions of synthetic chromatin in living systems.