title: Phosphorylation of histone H3(T118) alters nucleosome dynamics and remodeling.
abstract: Nucleosomes, the fundamental units of chromatin structure, are regulators and barriers to transcription, replication and repair. Post-translational modifications (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 transcription 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 2  kcal/mol, increases nucleosome mobility by 28-fold and increases DNA accessibility near the dyad region by 6-fold. Moreover, H3(T118ph) increases the rate of hMSH2-hMSH6 nucleosome disassembly and enables nucleosome disassembly by the SWI/SNF chromatin remodeler. These studies suggest that H3(T118ph) directly enhances and may reprogram chromatin remodeling reactions.
authors.affiliation: Department of Physics, The Ohio State University and The Ohio State University Medical Center, Columbus, OH 43210, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: North
authors.forename: Sarah
authors.initials: S
authors.lastname: Javaid
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Ferdinand
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Picking
authors.forename: Matthew
authors.initials: M
authors.lastname: Shoffner
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Nakkula
authors.forename: Blaine
authors.initials: B
authors.lastname: Bartholomew
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Ottesen
authors.forename: Richard
authors.initials: R
authors.lastname: Fishel
authors.forename: Michael G
authors.initials: MG
authors.lastname: Poirier
mesh_terms: D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D006657:Histones; D009707:Nucleosomes; D004247:DNA; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein