title: Dynamic and flexible H3K9me3 bridging via HP1β dimerization establishes a plastic state of condensed chromatin.
abstract: Histone H3 trimethylation of lysine 9 (H3K9me3) and proteins of the heterochromatin protein 1 (HP1) family are hallmarks of heterochromatin, a state of compacted DNA essential for genome stability and long-term transcriptional silencing. The mechanisms by which H3K9me3 and HP1 contribute to chromatin condensation have been speculative and controversial. Here we demonstrate that human HP1β is a prototypic HP1 protein exemplifying most basal chromatin binding and effects. These are caused by dimeric and dynamic interaction with highly enriched H3K9me3 and are modulated by various electrostatic interfaces. HP1β bridges condensed chromatin, which we postulate stabilizes the compacted state. In agreement, HP1β genome-wide localization follows H3K9me3-enrichment and artificial bridging of chromatin fibres is sufficient for maintaining cellular heterochromatic conformation. Overall, our findings define a fundamental mechanism for chromatin higher order structural changes caused by HP1 proteins, which might contribute to the plastic nature of condensed chromatin.
authors.affiliation: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Am Fassberg 11, 37077, Germany.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hiragami-Hamada
authors.affiliation: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Am Fassberg 11, 37077, Germany.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Soeroes
authors.affiliation: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Am Fassberg 11, 37077, Germany.|Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, Göttingen, Am Fassberg 11, 37077, Germany.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Nikolov
authors.affiliation: Applied Synthetic Biology, Institute for Microbiology and Genetics, Georg-August University Göttingen, 37077 Göttingen, Germany.
authors.forename: Bryan
authors.initials: B
authors.lastname: Wilkins
authors.affiliation: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Am Fassberg 11, 37077, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kreuz
authors.affiliation: Department of Medical Genetics, Life Sciences Institute, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
authors.forename: Carol
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
authors.forename: Inti A
authors.initials: IA
authors.lastname: De La Rosa-Velázquez
authors.affiliation: Biaffin GmbH &Co KG, Heinrich-Plett Strasse 40, 34132 Kassel, Germany.
authors.forename: Hans Michael
authors.initials: HM
authors.lastname: Zenn
authors.affiliation: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Am Fassberg 11, 37077, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Kost
authors.affiliation: Biomolecular Spectroscopy and Single-Molecule Detection, Max Planck Institute for Biophysical Chemistry, Göttingen, Am Fassberg 11, 37077, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Pohl
authors.affiliation: Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, Göttingen, Am Fassberg 11, 37077, Germany.|Bioanalytics, Institute for Clinical Chemistry, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Chernev
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str. 4, 72076 Tübingen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schwarzer
authors.affiliation: Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jenuwein
authors.affiliation: Department of Medical Genetics, Life Sciences Institute, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
authors.forename: Matthew
authors.initials: M
authors.lastname: Lorincz
authors.affiliation: Biaffin GmbH &Co KG, Heinrich-Plett Strasse 40, 34132 Kassel, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Zimmermann
authors.affiliation: Biomolecular Spectroscopy and Single-Molecule Detection, Max Planck Institute for Biophysical Chemistry, Göttingen, Am Fassberg 11, 37077, Germany.|Department of Biophysical Chemistry, Technische Universität Braunschweig, Hans-Sommerstr. 10, 38106 Braunschweig, Germany.
authors.forename: Peter Jomo
authors.initials: PJ
authors.lastname: Walla
authors.affiliation: Applied Synthetic Biology, Institute for Microbiology and Genetics, Georg-August University Göttingen, 37077 Göttingen, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Neumann
authors.affiliation: Department of Molecular Mechanisms of Disease, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors.forename: Tuncay
authors.initials: T
authors.lastname: Baubec
authors.affiliation: Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, Göttingen, Am Fassberg 11, 37077, Germany.|Bioanalytics, Institute for Clinical Chemistry, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.affiliation: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Am Fassberg 11, 37077, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Fischle
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D008745:Methylation; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: C000715593:CBX1 protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D009707:Nucleosomes; D000090266:Chromobox Protein Homolog 5; D008239:Lysine