Facile semisynthesis of histone H3 enables nucleosome probes for investigation of histone H_(3)K79 modifications  

作　　者：Kun Zou Yihang Xiao jinyu Yang Mingxuan Wu 

机构地区：[1]Department of Chemistry,Zhejiang University,Hangzhou 310027,China [2]Department of Chemistry,School of Science,Westlake University,Hangzhou 310030,China [3]Institute of Natural Sciences,Westlake Institute for Advanced Study,Hangzhou 310024,China

出　　处：《Chinese Chemical Letters》2024年第10期321-324,共4页中国化学快报（英文版）

基　　金：support from National Natural Science Foundation of China(Nos.22077103 and 22161132006);Westlake University startup。

摘　　要：Histone H3K79 modifications are essential to regulate chromatin structure and gene transcription,but understanding of the molecular mechanisms is limited.Because H3K79 is at globular domain,short histone peptide cannot mimic H3K79 in chromatin.Instead,reconstituted nucleosome-based chemical tools are ideally used to investigate H3K79 modifications.In consequence,H3K79-modified histone H3 with additional chemical handles are required,but such synthesis is challenging and laborious.Here we report a facile semisynthesis method that enables multifunctional histone H3 readily available.H3K79-containing fragment is short for straight peptide synthesis that was later ligated to recombinant expressed H3 fragments for full-length product in large scale.As a result,nucleosomes with H3K79 modifications as well as photo-reactive group and affinity tag were obtained to investigate potential binding proteins.We believe this method that enhances synthetic accessibility of nucleosome probes will accelerate understanding of the underexplored H3K79 modifications.

关 键 词：HISTONE H3K79 modifications METHYLATION SUCCINYLATION SEMISYNTHESIS Nucleosome probes 

分 类 号：Q343.2[生物学—遗传学] O657.3[理学—分析化学]