Department of Chemistry, University of Washington, Seattle, WA 98195, United States.
Department of Chemistry, University of Washington, Seattle, WA 98195, United States.
Curr Opin Chem Biol. 2018 Aug;45:27-34. doi: 10.1016/j.cbpa.2018.02.005. Epub 2018 Feb 27.
Reversible post-translational modifications of histone proteins in eukaryotic chromatin are closely tied to gene function and cellular development. Specific combinations of histone modifications, or marks, are implicated in distinct DNA-templated processes mediated by a range of chromatin-associated enzymes that install, erase and interpret the histone code. Mechanistic studies of the precise biochemical relationship between sets of marks and their effects on chromatin function are significantly complicated by the dynamic nature and heterogeneity of marks in cellular chromatin. Protein semisynthesis is a chemical technique that enables the piecewise assembly of uniformly and site-specifically modified histones in quantities sufficient for biophysical and biochemical analyses. Recent pioneering efforts in semisynthesis have yielded access to histones site-specifically modified by entire proteins, such as ubiquitin (Ub) and the small ubiquitin-like modifier (SUMO). Herein, we highlight key studies of biochemical crosstalk involving Ub and SUMO in chromatin that were enabled by histone semisynthesis.
真核染色质中组蛋白蛋白的翻译后可逆修饰与基因功能和细胞发育密切相关。特定的组蛋白修饰（或标记）组合与一系列染色质相关酶介导的不同 DNA 模板过程有关，这些酶可以安装、擦除和解释组蛋白密码。由于细胞染色质中标记的动态性质和异质性，对标记之间的精确生化关系及其对染色质功能影响的机制研究变得非常复杂。蛋白质半合成是一种化学技术，它能够在足够的数量上，逐步组装均匀和位点特异性修饰的组蛋白，用于生物物理和生物化学分析。最近在半合成方面的开创性工作已经获得了整个蛋白质（如泛素 (Ub) 和小泛素样修饰物 (SUMO)）特异性修饰的组蛋白。本文中，我们重点介绍了通过组蛋白半合成实现的涉及染色质中 Ub 和 SUMO 的生化串扰的关键研究。
