H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming (original) (raw)

Nature Structural & Molecular Biology volume 16, pages 777–781 (2009)Cite this article

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Abstract

Histone modifications are central to the regulation of all DNA-dependent processes. Lys64 of histone H3 (H3K64) lies within the globular domain at a structurally important position. We identify trimethylation of H3K64 (H3K64me3) as a modification that is enriched at pericentric heterochromatin and associated with repeat sequences and transcriptionally inactive genomic regions. We show that this new mark is dynamic during the two main epigenetic reprogramming events in mammals. In primordial germ cells, H3K64me3 is present at the time of specification, but it disappears transiently during reprogramming. In early mouse embryos, it is inherited exclusively maternally; subsequently, the modification is rapidly removed, suggesting an important role for H3K64me3 turnover in development. Taken together, our findings establish H3K64me3 as a previously uncharacterized histone modification that is preferentially localized to repressive chromatin. We hypothesize that H3K64me3 helps to 'secure' nucleosomes, and perhaps the surrounding chromatin, in an appropriately repressed state during development.

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In this article, the Ponceau staining presented in Fig. 1b (right, bottom) does not follow best practices for figure preparation since it inadvertently included duplications from the Ponceau staining presented in Supplementary Fig. 1b (for which the same preparation of nucleosomes from HeLa cells had been used). A new Fig. 1b is provided in the Author Correction.

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Acknowledgements

Work in the R.S. laboratory is supported by the Max Planck Society, the Deutsche Forschungsgemeinschaft (through SFB 746), Human Frontier Science Program, the EU (the Epigenome) and a European Research Council starting grant. We are grateful to T. Jenuwein (Max Planck Institute, Freiburg) for providing Suv39dn MEFs. We thank L. Tora for support. M.-E.T.-P. acknowledges funding from Avenir and PNRRE/INSERM.

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Author notes

  1. Thomas Weiss and Fabio Mohn: These authors contributed equally to this work.

Authors and Affiliations

  1. Max-Planck-Institute for Immunobiology, Freiburg, Germany
    Sylvain Daujat, Thomas Weiss, Ulrike C Lange, Ulrike Zeissler & Robert Schneider
  2. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    Fabio Mohn & Dirk Schübeler
  3. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS/INSERM/ULP, Strasbourg, France
    Céline Ziegler-Birling & Maria-Elena Torres-Padilla
  4. Max-Planck-Institute for Molecular Genetics, Berlin, Germany
    Michael Lappe

Authors

  1. Sylvain Daujat
  2. Thomas Weiss
  3. Fabio Mohn
  4. Ulrike C Lange
  5. Céline Ziegler-Birling
  6. Ulrike Zeissler
  7. Michael Lappe
  8. Dirk Schübeler
  9. Maria-Elena Torres-Padilla
  10. Robert Schneider

Corresponding author

Correspondence toRobert Schneider.

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Daujat, S., Weiss, T., Mohn, F. et al. H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming.Nat Struct Mol Biol 16, 777–781 (2009). https://doi.org/10.1038/nsmb.1629

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