Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
Greater Bay Biomedical InnoCenter, Shenzhen Bay Laboratory, Shenzhen 518055, China.
J Am Chem Soc. 2022 Nov 23;144(46):20979-20997. doi: 10.1021/jacs.2c06135. Epub 2022 Nov 8.
Covalent modifications of DNA and histones are key cellular epigenetic marks to regulate gene functions. Most of these epigenetic marks are added or removed by corresponding enzymes known as writers and erasers, whose catalytic activities normally rely on the presence of cellular metabolites as cofactors. Epigenetic marks can either directly alter the chromatin structure and dynamics through changing the intra-/internucleosomal histone-histone and histone-DNA interactions or recruit readers that further bring in other proteins with chromatin-modifying/remodeling activities to reshape the local and regional chromatin organization. In these two ways, epigenetic modifications modulate diverse DNA-templated processes, such as gene transcription, DNA replication, and DNA damage repair. Therefore, elucidation of the regulatory mechanisms and biological significance of epigenetic marks requires the identification and characterization of the protein-protein, protein-nucleic acid, and protein-small molecule interactions that control the underlying epigenetic processes. Here, we review the recent advances in using photo-cross-linking strategies to interrogate the epigenetic interactome, focusing on the protein-protein interactions mediated by epigenetic marks in histone tails. We also discuss future directions of developing photo-cross-linking-based tools and methods toward the investigation of the binding events in nucleosomal/chromatinic contexts, and toward the capture of the epigenetic interactome in live cells or even organisms.
DNA 和组蛋白的共价修饰是调节基因功能的关键细胞表观遗传标记。这些表观遗传标记中的大多数是由相应的酶（称为写入器和橡皮擦）添加或去除的，其催化活性通常依赖于细胞代谢物作为辅因子的存在。表观遗传标记可以通过改变核小体间的组蛋白-组蛋白和组蛋白-DNA 相互作用，直接改变染色质结构和动力学，或者招募读取器，进一步将具有染色质修饰/重塑活性的其他蛋白质引入，以重塑局部和区域染色质组织。通过这两种方式，表观遗传修饰调节多种 DNA 模板过程，如基因转录、DNA 复制和 DNA 损伤修复。因此，阐明表观遗传标记的调控机制和生物学意义需要鉴定和表征控制潜在表观遗传过程的蛋白质-蛋白质、蛋白质-核酸和蛋白质-小分子相互作用。在这里，我们综述了使用光交联策略来研究表观遗传互作组的最新进展，重点介绍了由组蛋白尾部上的表观遗传标记介导的蛋白质-蛋白质相互作用。我们还讨论了开发基于光交联的工具和方法的未来方向，用于研究核小体/染色质环境中的结合事件，以及用于在活细胞甚至生物体中捕获表观遗传互作组。
