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Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component

Nature Genetics volume 30, pages 329334 (2002) | Download Citation

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Abstract

Post-translational modification of histone tails is thought to modulate higher-order chromatin structure1,2,3. Combinations of modifications including acetylation, phosphorylation and methylation have been proposed to provide marks recognized by specific proteins4. This is exemplified, in both mammalian cells and fission yeast, by transcriptionally silent constitutive pericentric heterochromatin. Such heterochromatin contains histones that are generally hypoacetylated5 and methylated by Suv39h methyltransferases at lysine 9 of histone H3 (H3-K9)6,7. Each of these modification states has been implicated in the maintenance of HP1 protein–binding at pericentric heterochromatin, in transcriptional silencing and in centromere function7,8,9,10,11,12. In particular, H3-K9 methylation is thought to provide a marking system for the establishment and maintenance of stably repressed regions and heterochromatin subdomains3,13. To address the question of how these two types of modifications, as well as other unidentified parameters, function to maintain pericentric heterochromatin, we used a combination of histone deacetylase inhibitors, RNAse treatments and an antibody raised against methylated branched H3-K9 peptides. Our results show that both H3-K9 acetylation and methylation can occur on independent sets of H3 molecules in pericentric heterochromatin. In addition, we identify an RNA- and histone modification–dependent structure that brings methylated H3-K9 tails together in a specific configuration required for the accumulation of HP1 proteins in these domains.

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Acknowledgements

We thank W. Earnshaw for the HP1α-GST clone, B. Dietrich, C. Green and E. Heard for critical reading, and A. Kohlmaier for help with the protein analysis of histone modifications in Suv39h double-negative PMEFs. Work in T.J.'s laboratory is supported by the Institute of Molecular Pathology through Boehringer Ingelheim and grants from the Austrian Research promotion fund, the Vienna Economy Promotion Fund and a European Union Intellectual Property network grant. Research in G.A.'s laboratory is supported by Ligue Nationale Contre le Cancer, Euratom and an EU Improving Human Potential network grant.

Author information

Author notes

    • Angela Taddei

    Present address: University of Geneva, Geneva, Switzerland.

Affiliations

  1. Institut Curie, Research section, UMR 218 du CNRS, 26 rue d'Ulm, 75248 Paris cedex 05, France.

    • Christèle Maison
    • , Delphine Bailly
    • , Jean-Pierre Quivy
    • , Danièle Roche
    • , Angela Taddei
    •  & Geneviève Almouzni
  2. Research Institute of Molecular Pathology, The Vienna Biocenter, Dr Borghasse 7, A-1030 Vienna, Austria.

    • Antoine H.F.M. Peters
    • , Monika Lachner
    •  & Thomas Jenuwein

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Geneviève Almouzni.

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DOI

https://doi.org/10.1038/ng843

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