Methylation of lysine 9 in histone H3 directs alternative modes of highly dynamic interaction of heterochromatin protein hHP1β with the nucleosome

Francesca Munari, Szabolcs Soeroes, Hans Michael Zenn, Adrian Schomburg, Nils Kost, Sabrina Schröder, Rebecca Klingberg, Nasrollah Rezaei-Ghaleh, Alexandra Stützer, Kathy Ann Gelato, Peter Jomo Walla, Stefan Becker, Dirk Schwarzer, Bastian Zimmermann, Wolfgang Fischle*, Markus Zweckstetter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)33756-33765
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number40
DOIs
StatePublished - Sep 28 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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