Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK.
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK; Department of Biochemistry, University of Oxford, New Biochemistry Building, South Parks Road, Oxford, OX1 3QU, UK.
Curr Opin Chem Biol. 2018 Aug;45:35-47. doi: 10.1016/j.cbpa.2018.02.004. Epub 2018 Feb 28.
Chromatin is the physiological template of genetic information in all eukaryotic cells, a highly organised complex of DNA and histone proteins central in regulating gene expression and genome organisation. A multitude of histone post-translational modifications (PTMs) have been discovered, providing a glance into the complex interplay of these epigenetic marks in cellular processes. In the last decade, synthetic and chemical biology techniques have emerged to study these modifications, including genetic code expansion, histone semisynthesis and post-translational chemical mutagenesis. These methods allow for the creation of histones carrying synthetic modifications which can in turn be assembled into designer nucleosomes. Their application in vitro and in vivo is now beginning to have an important impact on chromatin biology. Efforts towards introducing multiple labile modifications in histones as well as expanding their use in cellular biology promise new powerful tools to study epigenetics.
染色质是所有真核细胞中遗传信息的生理模板，是 DNA 和组蛋白等蛋白质高度组织化的复合物，在调节基因表达和基因组组织中起着核心作用。已经发现了许多组蛋白翻译后修饰（PTMs），为研究这些表观遗传标记在细胞过程中的复杂相互作用提供了线索。在过去的十年中，合成和化学生物学技术已经出现，用于研究这些修饰，包括遗传密码扩展、组蛋白半合成和翻译后化学诱变。这些方法允许创建携带合成修饰的组蛋白，这些组蛋白可以进一步组装成设计的核小体。它们在体外和体内的应用现在开始对染色质生物学产生重要影响。努力在组蛋白中引入多种不稳定的修饰，并扩大它们在细胞生物学中的应用，有望为研究表观遗传学提供新的强大工具。
