Role of histone variant and histone tails within the nucleosome and the impact of H3 tail acetylation studied using enhanced sampling simulation

拡張サンプリング法によるヒストンバリアントとそのアセチル化の影響解析

池部 仁善; Li, Z.; 桜庭 俊*; 石田 恒; 河野 秀俊

Ikebe, Kimiyoshi; Li, Z.; Sakuraba, Shun*; Ishida, Hisashi; Kono, Hidetoshi

Nucleosome is the fundamental structural unit of chromatin. Histone proteins which constitute the nucleosome have their variants. In addition, histone proteins are subject to post-translational modification (PTM) to function in epigenetics. Acetylation of histone tails generally functions to activate gene expression, though the molecular mechanism is not well understood. We carried out conventional molecular dynamics simulations and enhanced sampling simulation to examine the impact of histone variant and the acetylation on the stability and dynamics of nucleosome. The results suggest that (1) stability of nucleosome depends on constituted histones; (2) N-terminal tail of H3 and C-terminal tail of H2A are both associated with dynamics of liker DNA and (3) acetylation makes the H3 tail conformation more compact and enhances dissociation of nucleosomal DNA from the histone core. Further, the acetylated lysine was more exposed to the solvent, which is consistent with its role as a PTM recognition site marker. These findings increase our understanding of role of histone variants and the impact of PTM on nucleosome stability and dynamics and on the higher order structure of chromatin.