Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Meeting Report
  • Published:

Defining epigenetic states through chromatin and RNA

Nature Genetics volume 37, pages 917–918 (2005)Cite this article

Nucleosomal histones are the target of a variety of post-translational modifications, including acetylation, phosphorylation, ubiquitination and methylation. These alterations regulate accessibility for DNA binding proteins and create recognition signals to anchor protein complexes. Despite intensive study, we know little about how the bulk of the potential modification repertoire is used, what the function of individual or combined modifications is or how modifications are targeted to specific domains or loci. One recent research focus is the dynamics of histone methylation, involved in both gene activation and repression, depending on the modified amino acid. The extent of modification can vary, for example, between mono-, di- and trimethylated lysine. Methylation at Lys4 of histone H3 (H3K4me), typical of the active state, is mediated in vertebrates by the complexes MLL1, MLL2 and hSet1, which all share the WD40 domain protein WDR5. Joanna Wysocka (New York, USA; with C. David Allis, New York, USA) showed that WDR5 directly interacts with H3K4me2 and can enhance transcription if tethered to a reporter gene. Knock-down of WDR5 leads to selective reduction of H3K4me3, as opposed to H3K4me2, but does lead to developmental defects in Xenopus laevis embryos. As a cofactor required for H3K4me3, WDR5 may help to propagate an active state by both recognizing the dimethylated form and promoting trimethylation, providing a parallel to the well-known role of HP1 in supporting heterochromatin formation2. Such patterns of interaction between modified histones and histone modifiers may be inherent to epigenetic regulation of gene expression at the domain level, a paradigm distinct from those operating in prokaryotes.

Modification of neighboring residues can block or enhance individual histone modifications, suggestive of obligate pathways of modification with enhanced regulatory potential. In a new twist, Tony Kouzarides (Cambridge, UK) discussed the impact of proline isomerization on H3K36me, a modification that has been implicated in regulation of the elongating RNA polymerase II3. Peptidyl-prolyl-isomerases catalyze the conversion of proline from cis to trans form, altering the peptide backbone configuration. The enzyme FPR4 can isomerize H3 Pro38 in vitro; Pro38 appears to be required for K36me in vivo. This result suggests that the cis-trans isomerization of proline peptide bonds could be a regulated process that might occur upstream of covalent histone modification.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Ahktar, A. & Cavelli, G. The epigenome network of excellence. PLoS Biol. 3, e177 (2005).

    Article  Google Scholar 

  2. Wysocka, J. et al. WDR5 associaties with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell 121, 859–872 (2005).

    Article  CAS  Google Scholar 

  3. Xiao, T. et al. Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast. Genes Dev. 17, 654–663 (2003).

    Article  CAS  Google Scholar 

  4. Henikoff, S., Furuyama, T. & Ahmad, K. Histone variants, nucleosome assembly and epigenetic inheritance. Trends Genet. 20, 320–326 (2004).

    Article  CAS  Google Scholar 

  5. Wolffe, A.P. Centromeric chromatin. Histone deviants. Curr. Biol. 5, 452–454 (1995).

    Article  CAS  Google Scholar 

  6. Herr, A.J., Jensen, M.B., Dalmay, T. & Baulcombe, D.C. RNA polymerase IV directs silencing of endogenous DNA. Science 308, 118–120 (2005).

    Article  CAS  Google Scholar 

  7. Onodera, Y. et al. Plant nuclear RNA polymerase IV mediates siRNA and DNA methylation-dependent heterochromatin formation. Cell 120, 613–622 (2005).

    Article  CAS  Google Scholar 

  8. Kanno, T. et al. Atypical RNA polymerase subunits required for RNA-directed DNA methylation. Nat. Genet. 37, 761–765 (2005).

    Article  CAS  Google Scholar 

  9. Pontier, D. et al. Reinforcement of silencing at transposon and highly repeated sequences requires the concerted action of two distinct RNA polymerases IV in Arabidopsis. Genes Dev. (in the press).

  10. Davis, E. et al. RNAi-mediated allelic trans-interaction at the imprinted Rtl1/Peg11 locus. Curr. Biol. 15, 743–749 (2005).

    Article  CAS  Google Scholar 

  11. Ishii, K., Arib, G., Lin, C., Van Houwe, G. & Laemmli, U.K. Chromatin boundaries in budding yeast: the nuclear pore connection. Cell 109, 551–562 (2002).

    Article  CAS  Google Scholar 

  12. Casolari, J.M., Brown, C.R., Drubin, D.A., Rando, O.J. & Silver, P.A. Developmentally induced changes in transcriptional program alter spatial organization across chromosomes. Genes Dev. 19, 1188–1198 (2005).

    Article  CAS  Google Scholar 

  13. Greiner, D., Bonaldi, T., Ekeland, R., Roemer, E. & Imhof, A. Identification of a specific inhibitor of histone methyltransferases of the SUV39 family. Nat. Chem. Biol. 1, 143–145 (2005).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Friedrich Miescher Institute for Biomedical Research, Basel, 4058, Switzerland

    Dirk Schübeler

  2. Department of Biology, Washington University, St. Louis, 63130, Missouri, USA

    Sarah C R Elgin

Authors
  1. Dirk Schübeler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah C R Elgin
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schübeler, D., Elgin, S. Defining epigenetic states through chromatin and RNA. Nat Genet 37, 917–918 (2005). https://doi.org/10.1038/ng0905-917

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0905-917

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing