title: Regulation of the nucleosome unwrapping rate controls DNA accessibility.
abstract: Eukaryotic genomes are repetitively wrapped into nucleosomes that then regulate access of transcription and DNA repair complexes to DNA. The mechanisms that regulate extrinsic protein interactions within nucleosomes are unresolved. We demonstrate that modulation of the nucleosome unwrapping rate regulates protein binding within nucleosomes. Histone H3 acetyl-lysine 56 [H3(K56ac)] and DNA sequence within the nucleosome entry-exit region additively influence nucleosomal DNA accessibility by increasing the unwrapping rate without impacting rewrapping. These combined epigenetic and genetic factors influence transcription factor (TF) occupancy within the nucleosome by at least one order of magnitude and enhance nucleosome disassembly by the DNA mismatch repair complex, hMSH2-hMSH6. Our results combined with the observation that ∼30% of Saccharomyces cerevisiae TF-binding sites reside in the nucleosome entry-exit region suggest that modulation of nucleosome unwrapping is a mechanism for regulating transcription and DNA repair.
authors.affiliation: Department of Physics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: North
authors.forename: John C
authors.initials: JC
authors.lastname: Shimko
authors.forename: Sarah
authors.initials: S
authors.lastname: Javaid
authors.forename: Alex M
authors.initials: AM
authors.lastname: Mooney
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Shoffner
authors.forename: Sean D
authors.initials: SD
authors.lastname: Rose
authors.forename: Ralf
authors.initials: R
authors.lastname: Bundschuh
authors.forename: Richard
authors.initials: R
authors.lastname: Fishel
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Ottesen
authors.forename: Michael G
authors.initials: MG
authors.lastname: Poirier
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006657:Histones; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D006657:Histones; D009707:Nucleosomes; D014157:Transcription Factors; D004247:DNA; D051718:MutS Homolog 2 Protein