title: Histone Acetylation Regulates Chromatin Accessibility: Role of H4K16 in Inter-nucleosome Interaction.
abstract: The N-terminal tail of histone H4 is an indispensable mediator for inter-nucleosome interaction, which is required for chromatin fiber condensation. H4K16 acetylation (H4K16Ac) activates gene transcription by influencing both chromatin structure and interplay with nonhistone proteins. To understand the influence of H4K16Ac on inter-nucleosome interaction, we performed a simulation study for the H4 tail in the context of two nucleosomes in neighboring unit cells in the crystal structure. The binding conformation of H4 tail with/without K16Ac was sampled by replica exchange with solute tempering, and the free energy landscape was explored by metadynamics. The results indicate two important features of H4K16: 1) it is the first button to anchor the H4 tail on the adjacent nucleosome; and 2) it is the only acetylation site interacting with the acidic patch. H4K16Ac disrupts the electrostatic interactions of K16, weakens H4 tail-acidic patch binding, and significantly increases H4 tail conformation diversity. Our study suggests that H4K16Ac directly reduces the inter-nucleosome interaction mediated by the H4 tail, which might further encourage the binding of nonhistone proteins on the acidic patch.
authors.affiliation: Division Biophysics of Macromolecules, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Ruihan
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Division Biophysics of Macromolecules, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Erler
authors.affiliation: Division Biophysics of Macromolecules, German Cancer Research Center, Heidelberg, Germany. Electronic address: jl@dkfz.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Langowski
mesh_terms: D000107:Acetylation; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008239:Lysine / Q000378:metabolism*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000378:metabolism*; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary
chemical_list: D006657:Histones; D009707:Nucleosomes; D008239:Lysine