Phosphorylation of histone H3(T118) alters nucleosome dynamics and remodeling

Nucleosomes, the fundamental units of chromatin structure, are regulators and barriers to transcrip-tion, replication and repair. Post-translational modi-fications (PTMs) of the histone proteins within nucleosomes regulate these DNA processes. Histone H3(T118) is a site of phosphorylation [H3(T118ph)] and is implicated in regulation of tran-scription and DNA repair. We prepared H3(T118ph) by expressed protein ligation and determined its influence on nucleosome dynamics. We find H3(T118ph) reduces DNA–histone binding by 2kcal/mol, increases nucleosome mobility by 28-fold and increases DNA accessibility near the dyad region by 6-fold. Moreover, H3(T118ph) in-creases the rate of hMSH2–hMSH6 nucleosome dis-assembly and enables nucleosome disassembly by the SWI/SNF chromatin remodeler. These studies suggest that H3(T118ph) directly enhances and may reprogram chromatin remodeling reactions