title: Modulations of DNA Contacts by Linker Histones and Post-translational Modifications Determine the Mobility and Modifiability of Nucleosomal H3 Tails.
abstract: Post-translational histone modifications and linker histone incorporation regulate chromatin structure and genome activity. How these systems interface on a molecular level is unclear. Using biochemistry and NMR spectroscopy, we deduced mechanistic insights into the modification behavior of N-terminal histone H3 tails in different nucleosomal contexts. We find that linker histones generally inhibit modifications of different H3 sites and reduce H3 tail dynamics in nucleosomes. These effects are caused by modulations of electrostatic interactions of H3 tails with linker DNA and largely depend on the C-terminal domains of linker histones. In agreement, linker histone occupancy and H3 tail modifications segregate on a genome-wide level. Charge-modulating modifications such as phosphorylation and acetylation weaken transient H3 tail-linker DNA interactions, increase H3 tail dynamics, and, concomitantly, enhance general modifiability. We propose that alterations of H3 tail-linker DNA interactions by linker histones and charge-modulating modifications execute basal control mechanisms of chromatin function.
authors.affiliation: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stützer
authors.affiliation: Department of NMR-Supported Structural Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rössle Strasse 10, 13125 Berlin, Germany.
authors.forename: Stamatios
authors.initials: S
authors.lastname: Liokatis
authors.affiliation: Research Group of Computational Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Kiesel
authors.affiliation: Department of Chemical Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rössle Strasse 10, 13125 Berlin, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schwarzer
authors.affiliation: Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen, Germany.
authors.forename: Remco
authors.initials: R
authors.lastname: Sprangers
authors.affiliation: Research Group of Computational Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany; Gene Center and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Söding
authors.affiliation: Department of NMR-Supported Structural Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rössle Strasse 10, 13125 Berlin, Germany. Electronic address: selenko@fmp-berlin.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Selenko
authors.affiliation: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: wfischl@mpibpc.mpg.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Fischle
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000378:metabolism*; D016678:Genome; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D014982:Xenopus laevis
chemical_list: D006657:Histones; D009707:Nucleosomes; D004247:DNA