近日，北京大学陈鹏等研究人员合作
研究人员开发了一种单点分辨的多组学（SiTomics）策略，用于系统地绘制动态修饰图谱，并随后对染色质化的蛋白质组和基因组进行剖析，该策略由活细胞中特定的染色质乙酰化定义。通过利用遗传密码扩展策略，这个SiTomics工具箱揭示了短链脂肪酸刺激下不同的巴豆酰化（如H3K56cr）和β-羟基丁酰化（如H3K56bhb），并为染色质酰化标记定义的蛋白质组、基因组和功能建立了联系。这导致了GLYR1成为调节H3K56cr′s基因体定位的一个独特的相互作用蛋白，并发现了bhb介导的染色质调控所依据的超级增强器曲目的提升。SiTomics提供了一个阐明“代谢物-修饰-调控”轴的平台技术，广泛适用于多组学分析和对酰化以外的修饰和组蛋白以外的蛋白质进行功能剖析。
据了解，一个具有可编程位点特异性的通用策略，用于对未受干扰的染色质上的组蛋白修饰进行原位分析，仍然是非常理想的，但具有挑战性。
附：英文原文
Title: Linking chromatin acylation mark-defined proteome and genome in living cells
Author: Fangfei Qin, Boyuan Li, Hui Wang, Sihui Ma, Jiaofeng Li, Shanglin Liu, Linghao Kong, Huangtao Zheng, Rongfeng Zhu, Yu Han, Mingdong Yang, Kai Li, Xiong Ji, Peng R. Chen
Issue&Volume: 2023/03/02
Abstract: A generalizable strategy with programmable site specificity for in situ profiling of histone modifications on unperturbed chromatin remains highly desirablebut challenging. We herein developed a single-site-resolved multi-omics (SiTomics)strategy for systematic mapping of dynamic modifications and subsequent profilingof chromatinized proteome and genome defined by specific chromatin acylations in livingcells. By leveraging the genetic code expansion strategy, our SiTomics toolkit revealeddistinct crotonylation (e.g., H3K56cr) and β-hydroxybutyrylation (e.g., H3K56bhb) upon short chain fatty acids stimulation andestablished linkages for chromatin acylation mark-defined proteome, genome, and functions.This led to the identification of GLYR1 as a distinct interacting protein in modulatingH3K56cr′s gene body localization as well as the discovery of an elevated super-enhancerrepertoire underlying bhb-mediated chromatin modulations. SiTomics offers a platformtechnology for elucidating the “metabolites-modification-regulation” axis, which iswidely applicable for multi-omics profiling and functional dissection of modificationsbeyond acylations and proteins beyond histones.
DOI: 10.1016/j.cell.2023.02.007
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00109-5