title: Histone fold modifications control nucleosome unwrapping and disassembly.
abstract: Nucleosomes are stable DNA-histone protein complexes that must be unwrapped and disassembled for genome expression, replication, and repair. Histone posttranslational modifications (PTMs) are major regulatory factors of these nucleosome structural changes, but the molecular mechanisms associated with PTM function remains poorly understood. Here we demonstrate that histone PTMs within distinct structured regions of the nucleosome directly regulate the inherent dynamic properties of the nucleosome. Precise PTMs were introduced into nucleosomes by chemical ligation. Single molecule magnetic tweezers measurements determined that only PTMs near the nucleosome dyad increase the rate of histone release in unwrapped nucleosomes. In contrast, FRET and restriction enzyme analysis reveal that only PTMs throughout the DNA entry-exit region increase unwrapping and enhance transcription factor binding to nucleosomal DNA. These results demonstrate that PTMs in separate structural regions of the nucleosome control distinct dynamic events, where the dyad regulates disassembly while the DNA entry-exit region regulates unwrapping. These studies are consistent with the conclusion that histone PTMs may independently influence nucleosome dynamics and associated chromatin functions.
authors.affiliation: Department of Physics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Marek
authors.initials: M
authors.lastname: Simon
authors.forename: Justin A
authors.initials: JA
authors.lastname: North
authors.forename: John C
authors.initials: JC
authors.lastname: Shimko
authors.forename: Robert A
authors.initials: RA
authors.lastname: Forties
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Ferdinand
authors.forename: Mridula
authors.initials: M
authors.lastname: Manohar
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
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: D000107:Acetylation; D000465:Algorithms; D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D031541:Fluorescence Resonance Energy Transfer; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008239:Lysine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D009154:Mutation; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes; D011994:Recombinant Proteins; D004247:DNA; D008239:Lysine