Nucleic Acids Research · 2010 · 201 citations · 59 references
Life SciencesBiochemistryMolecular BiologyChromatin BiologyChromatin StructureStructural BiologyChromatinHistone ProteinsMacromolecular AssemblyNucleosome DynamicsNucleosome OrganizationNucleosome StructureDimer InterfaceHistone H2a-h2b DimerIntermediate State CharacterizationNucleosome AccessibilityNucleosome AssemblyNucleosome DisassemblyOpen State TransitionsSingle-molecule Fret Analysis
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.
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Crystal structure of the nucleosome core particle at 2.8 Å resolution
Karolin Luger, Armin W. Mäder, Robin K. Richmond et al. · Nature · 1997 · 9.4K citations