title: Methylation of lysine 9 in histone H3 directs alternative modes of highly dynamic interaction of heterochromatin protein hHP1β with the nucleosome.
abstract: Binding of heterochromatin protein 1 (HP1) to the histone H3 lysine 9 trimethylation (H3K9me3) mark is a hallmark of establishment and maintenance of heterochromatin. Although genetic and cell biological aspects have been elucidated, the molecular details of HP1 binding to H3K9me3 nucleosomes are unknown. Using a combination of NMR spectroscopy and biophysical measurements on fully defined recombinant experimental systems, we demonstrate that H3K9me3 works as an on/off switch regulating distinct binding modes of hHP1β to the nucleosome. The methyl-mark determines a highly flexible and very dynamic interaction of the chromodomain of hHP1β with the H3-tail. There are no other constraints of interaction or additional multimerization interfaces. In contrast, in the absence of methylation, the hinge region and the N-terminal tail form weak nucleosome contacts mainly with DNA. In agreement with the high flexibility within the hHP1β-H3K9me3 nucleosome complex, the chromoshadow domain does not provide a direct binding interface. Our results report the first detailed structural analysis of a dynamic protein-nucleosome complex directed by a histone modification and provide a conceptual framework for understanding similar interactions in the context of chromatin.
authors: Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Francesca
authors: F
authors: Munari
authors: Szabolcs
authors: S
authors: Soeroes
authors: Hans Michael
authors: HM
authors: Zenn
authors: Adrian
authors: A
authors: Schomburg
authors: Nils
authors: N
authors: Kost
authors: Sabrina
authors: S
authors: Schröder
authors: Rebecca
authors: R
authors: Klingberg
authors: Nasrollah
authors: N
authors: Rezaei-Ghaleh
authors: Alexandra
authors: A
authors: Stützer
authors: Kathy Ann
authors: KA
authors: Gelato
authors: Peter Jomo
authors: PJ
authors: Walla
authors: Stefan
authors: S
authors: Becker
authors: Dirk
authors: D
authors: Schwarzer
authors: Bastian
authors: B
authors: Zimmermann
authors: Wolfgang
authors: W
authors: Fischle
authors: Markus
authors: M
authors: Zweckstetter
mesh_terms: D019921:Biotinylation; D002151:Calorimetry / Q000379:methods; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D044127:Epigenesis, Genetic; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008745:Methylation; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012568:Schizosaccharomyces / Q000378:metabolism
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009707:Nucleosomes; D000090266:Chromobox Protein Homolog 5; D004247:DNA; D008239:Lysine