title: Nucleosome accessibility governed by the dimer/tetramer interface.
abstract: Nucleosomes are multi-component macromolecular assemblies which present a formidable obstacle to enzymatic activities that require access to the DNA, e.g. DNA and RNA polymerases. The mechanism and pathway(s) by which nucleosomes disassemble to allow DNA access are not well understood. Here we present evidence from single molecule FRET experiments for a previously uncharacterized intermediate structural state before H2A-H2B dimer release, which is characterized by an increased distance between H2B and the nucleosomal dyad. This suggests that the first step in nucleosome disassembly is the opening of the (H3-H4)(2) tetramer/(H2A-H2B) dimer interface, followed by H2A-H2B dimer release from the DNA and, lastly, (H3-H4)(2) tetramer removal. We estimate that the open intermediate state is populated at 0.2-3% under physiological conditions. This finding could have significant in vivo implications for factor-mediated histone removal and exchange, as well as for regulating DNA accessibility to the transcription and replication machinery.
authors.affiliation: Abteilung Biophysik der Makromoleküle, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Böhm
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Hieb
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Andrews
authors.forename: Alexander
authors.initials: A
authors.lastname: Gansen
authors.forename: Andrea
authors.initials: A
authors.lastname: Rocker
authors.forename: Katalin
authors.initials: K
authors.lastname: Tóth
authors.forename: Karolin
authors.initials: K
authors.lastname: Luger
authors.forename: Jörg
authors.initials: J
authors.lastname: Langowski
mesh_terms: D042002:Chromatin Assembly and Disassembly; D031541:Fluorescence Resonance Energy Transfer; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism; D055503:Protein Multimerization; D012965:Sodium Chloride / Q000737:chemistry; D013050:Spectrometry, Fluorescence
chemical_list: D006657:Histones; D009707:Nucleosomes; D012965:Sodium Chloride