

Histochemie (Impact Factor: 2.61). 02/2006; 125(1-2):53-61. DOI:10.1007/s00418-005-0088-7
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    ABSTRACT: Although heterochromatin has long been used as a model for studying chromatin condensation and heritable gene silencing, it is only relatively recently that detailed information has become available on the mechanisms that underlie its structure. Current evidence suggests that these operate on at least three different levels. A regular nucleosome array may facilitate packaging of the chromatin into a highly condensed configuration. Methylation of histone H3 lysine 9 and lysine 27 generates heterochromatin marks that are recognised through binding of heterochromatin proteins such as HP1. Finally, very recent studies using genetic and biochemical approaches have indicated that the RNAi machinery plays an important role in the formation of heterochromatin.
    Biology of the Cell 11/2004; 96(8):631-7. · 3.49 Impact Factor
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    ABSTRACT: Distinct modifications of histone amino termini, such as acetylation, phosphorylation and methylation, have been proposed to underlie a chromatin-based regulatory mechanism 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 expression 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) generate a binding site for HP1 proteins--a family of heterochromatic adaptor molecules 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 lysine9 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 SWUV39H1 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.
    Nature 04/2001; 410(6824):116-20. · 38.60 Impact Factor
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    ABSTRACT: Heterochromatin protein 1 (HP1) is localized at heterochromatin sites where it mediates gene silencing. The chromo domain of HP1 is necessary for both targeting and transcriptional repression. In the fission yeast Schizosaccharomyces pombe, the correct localization of Swi6 (the HP1 equivalent) depends on Clr4, a homologue of the mammalian SUV39H1 histone methylase. Both Clr4 and SUV39H1 methylate specifically lysine 9 of histone H3 (ref. 6). Here we show that HP1 can bind with high affinity to histone H3 methylated at lysine 9 but not at lysine 4. The chromo domain of HP1 is identified as its methyl-lysine-binding domain. A point mutation in the chromo domain, which destroys the gene silencing activity of HP1 in Drosophila, abolishes methyl-lysine-binding activity. Genetic and biochemical analysis in S. pombe shows that the methylase activity of Clr4 is necessary for the correct localization of Swi6 at centromeric heterochromatin and for gene silencing. These results provide a stepwise model for the formation of a transcriptionally silent heterochromatin: SUV39H1 places a 'methyl marker' on histone H3, which is then recognized by HP1 through its chromo domain. This model may also explain the stable inheritance of the heterochromatic state.
    Nature 04/2001; 410(6824):120-4. · 38.60 Impact Factor

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