Conformational sampling of an acetylated histone tail with Adaptive Lambda Square Dynamics simulation

ALSDシミュレーションによるアセチル化されたヒストンテールの構造探索

池部 仁善; 桜庭 俊*; 河野 秀俊

Ikebe, Kimiyoshi; Sakuraba, Shun*; Kono, Hidetoshi

In eukaryotic cells, genome DNA forms nucleosomes composed of DNA wrapped around a histone octamer: two copies of H3, H4, H2A, and H2B histone proteins, and it is compactly stored in the nucleus. It is known that acetylation of lysine residues on H3 and H4 histone tails, which are N-terminal regions of H3 and H4 histone proteins, generally induces transcription. To elucidate the mechanism of the regulation, we performed conformational sampling of an acetylated H3 histone tail with Adaptive Lambda Square Dynamics (ALSD) simulation and compared the result with our previous simulation result of unacetylated H3 histone tail system. The results showed that H3 histone tail were almost always located nearby DNA regardless of the acetylation, which is against the conventional view that the acetylation is expected to cause major structural changes. However, the acetylation induced reduction of interactions between the histone tail and DNA and enhanced alpha helix formation of the histone tail. We infer that the histone tail compaction caused by the alpha helix formation induces unwrapping of DNA at entry/exit regions more and increases the chance of DNA-binding proteins bind to DNA. These results give a new view of how acetylation affects chromatin conformation.