Dynamic and flexible H3K9me3 bridging via HP1β dimerization establishes a plastic state of condensed chromatin

• DOI: 10.1038/ncomms11310
• Publication Date: 2016-04-19T10:12:03Z
• Authors: Kyoko Hiragami-Ha...; Szabolcs Soeroes; Miroslav Nikolov; Bryan Wilkins; Sarah Kreuz; Carol Chen; Inti A. De La Ros...; Hans Michael Zenn; Nils Kost; Wiebke Pohl; Aleksandar Chernev; Dirk Schwarzer; Thomas Jenuwein; Matthew Lorincz; Bastian Zimmermann; Peter Jomo Walla; Heinz Neumann; Tuncay Baubec; Henning Urlaub; Wolfgang Fischle
• Keywords: Models, Molecular; 0301 basic medicine; Chromosomal Proteins, Non-Histone; Science; Blotting, Western; Molecular Sequence Data; 1600 General Chemistry; Crystallography, X-Ray; Methylation; Article; Histones; 03 medical and health sciences; 1300 General Biochemistry, Genetics and Molecular Biology; Cell Line, Tumor; Heterochromatin; Humans; Amino Acid Sequence; Sequence Homology, Amino Acid; Lysine; Q; 10226 Department of Molecular Mechanisms of Disease; 3100 General Physics and Astronomy; Chromatin; Nucleosomes; Kinetics; Microscopy, Fluorescence; Chromobox Protein Homolog 5; 570 Life sciences; biology; Protein Multimerization; Protein Binding

AbstractHistone 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.