title: Histone acetylation dependent energy landscapes in tri-nucleosome revealed by residue-resolved molecular simulations.
abstract: Histone tail acetylation is a key epigenetic marker that tends to open chromatin folding and activate transcription. Despite intensive studies, precise roles of individual lysine acetylation in chromatin folding have only been poorly understood. Here, we revealed structural dynamics of tri-nucleosomes with several histone tail acetylation states and analyzed histone tail interactions with DNA by performing molecular simulations at an unprecedentedly high resolution. We found versatile acetylation-dependent landscapes of tri-nucleosome. The H4 and H2A tail acetylation reduced the contact between the first and third nucleosomes mediated by the histone tails. The H3 tail acetylation reduced its interaction with neighboring linker DNAs resulting in increase of the distance between consecutive nucleosomes. Notably, two copies of the same histone in a single nucleosome have markedly asymmetric interactions with DNAs, suggesting specific pattern of nucleosome docking albeit high inherent flexibility. Estimated transcription factor accessibility was significantly high for the H4 tail acetylated structures.
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Kitashirakawa, Sakyo 606-8502, Kyoto Japan.
authors.forename: Le
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Kitashirakawa, Sakyo 606-8502, Kyoto Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Takada
mesh_terms: D000107:Acetylation; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes; D004247:DNA