Department of Biochemistry , University of Iowa Carver College of Medicine , Iowa City , Iowa 52246 , United States.
Department of Pharmacology , University of Colorado School of Medicine , Aurora , Colorado 80045 , United States.
ACS Chem Biol. 2019 Apr 19;14(4):579-586. doi: 10.1021/acschembio.8b01049. Epub 2019 Mar 12.
Post-translational modifications on histone proteins play critical roles in the regulation of chromatin structure and all DNA-templated processes. Accumulating evidence suggests that these covalent modifications can directly alter chromatin structure, or they can modulate activities of chromatin-modifying and -remodeling factors. Studying these modifications in the context of the nucleosome, the basic subunit of chromatin, is thus of great interest; however, the generation of specifically modified nucleosomes remains challenging. This is especially problematic for most structural biology approaches in which a large amount of material is often needed. Here we discuss the strategies currently available for generation of these substrates. We in particular focus on novel ideas and discuss challenges in the application to structural biology studies.
组蛋白上的翻译后修饰在调节染色质结构和所有 DNA 模板过程中起着关键作用。越来越多的证据表明,这些共价修饰可以直接改变染色质结构,或者可以调节染色质修饰和重塑因子的活性。因此,在核小体(染色质的基本亚基)的背景下研究这些修饰具有重要意义;然而,产生特异性修饰的核小体仍然具有挑战性。对于大多数结构生物学方法来说,这是一个特别大的问题,因为这些方法通常需要大量的材料。在这里,我们讨论了目前可用于生成这些底物的策略。我们特别关注新的想法,并讨论了在应用于结构生物学研究中的挑战。