Letter | Published:

Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins

Nature volume 410, pages 116120 (01 March 2001) | Download Citation



Distinct modifications of histone amino termini, such as acetylation, phosphorylation and methylation, have been proposed to underlie a chromatin-based regulatory mechanism1,2 that modulates the accessibility of genetic information. In addition to histone modifications that facilitate gene activity, it is of similar importance to restrict inappropriate gene expression3,4 if cellular and developmental programmes are to proceed unperturbed. Here we show that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases)5 generate a binding site for HP1 proteins—a family of heterochromatic adaptor molecules6,7 implicated in both gene silencing and supra-nucleosomal chromatin structure. High-affinity in vitro recognition of a methylated histone H3 peptide by HP1 requires a functional chromo domain; thus, the HP1 chromo domain is a specific interaction motif for the methyl epitope on lysine 9 of histone H3. In vivo, heterochromatin association of HP1 proteins is lost in Suv39h double-null primary mouse fibroblasts but is restored after the re-introduction of a catalytically active SUV39H1 HMTase. Our data define a molecular mechanism through which the SUV39H–HP1 methylation system can contribute to the propagation of heterochromatic subdomains in native chromatin.

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We would like to thank M. Busslinger for the Pax5 cDNA; P. B. Singh for the HP1β (M31) and mPC1 (M33) cDNAs, and the HP1β antibodies; A. Verreault for the murine HP1α and HP1γ cDNAs; P. Chambon for HP1α antibodies; L. Huber for rabbit anti-Myc (9E10) antibodies; and Y. Zou for the MSCV–MIGR1 retroviral vectors. We acknowledge I. Gorny for help with peptide synthesis and M. Doyle for contributing to the Suv39h2 knock-out. We are grateful to D. Allis for discussions and to M. Busslinger for comments and critical reading of the manuscript. Research in T.J.'s laboratory is supported by the IMP through Boehringer Ingelheim, the Austrian Research Promotion Fund and the Vienna Economy Promotion Fund.

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    • Monika Lachner
    •  & Dónal O'Carroll

    These authors contributed equally to this work


  1. Research Institute of Molecular Pathology (IMP), The Vienna Biocenter, Dr Bohrgasse 7, A-1030 Vienna, Austria


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Correspondence to Thomas Jenuwein.

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