Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Boston, MA 02451, U.S.A.
Molecular, Cellular, and Biomedical Sciences, University of New Hampshire, Durham, NH 03824, U.S.A.
Biochem Soc Trans. 2021 Nov 1;49(5):2431-2441. doi: 10.1042/BST20210772.
Protein-protein interactions (PPIs) in the nucleus play key roles in transcriptional regulation and ensure genomic stability. Critical to this are histone-mediated PPI networks, which are further fine-tuned through dynamic post-translational modification. Perturbation to these networks leads to genomic instability and disease, presenting epigenetic proteins as key therapeutic targets. This mini-review will describe progress in mapping the combinatorial histone PTM landscape, and recent chemical biology approaches to map histone interactors. Recent advances in mapping direct interactors of histone PTMs as well as local chromatin interactomes will be highlighted, with a focus on mass-spectrometry based workflows that continue to illuminate histone-mediated PPIs in unprecedented detail.
核内的蛋白质-蛋白质相互作用 (PPIs) 在转录调控中发挥着关键作用，并确保基因组的稳定性。组蛋白介导的 PPI 网络对此至关重要，这些网络通过动态的翻译后修饰进一步精细调节。这些网络的破坏会导致基因组不稳定和疾病，使表观遗传蛋白成为关键的治疗靶点。这篇迷你评论将描述绘制组合组蛋白 PTM 图谱的进展，以及最近用于绘制组蛋白相互作用物的化学生物学方法。将重点介绍直接映射组蛋白 PTM 相互作用物以及局部染色质相互作用组的最新进展，重点是基于质谱的工作流程，这些工作流程继续以前所未有的细节阐明组蛋白介导的 PPI。
