Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription
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- Vincenzo Di Cerbo
- Department of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR, Strasbourg, France
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- Fabio Mohn
- Institute of Molecular Biotechnology, Vienna, Austria
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- Daniel P Ryan
- Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, United Kingdom
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- Emilie Montellier
- INSERM U823, Université Joseph Fourier, Grenoble, France
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- Salim Kacem
- Institut de Génétique Moléculaire, CNRS UMR5535/Université de Montpellier I and II, Montpellier, France
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- Philipp Tropberger
- Department of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR, Strasbourg, France
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- Eleni Kallis
- Institute for Biophysics, Ulm University, Ulm, Germany
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- Monika Holzner
- Institute for Biophysics, Ulm University, Ulm, Germany
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- Leslie Hoerner
- Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland
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- Angelika Feldmann
- Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland
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- Florian Martin Richter
- Cellular Immunobiology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
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- Andrew J Bannister
- Gurdon Institute, Cambridge, United Kingdom
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- Gerhard Mittler
- Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
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- Jens Michaelis
- Institute for Biophysics, Ulm University, Ulm, Germany
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- Saadi Khochbin
- INSERM U823, Université Joseph Fourier, Grenoble, France
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- Robert Feil
- Institut de Génétique Moléculaire, CNRS UMR5535/Université de Montpellier I and II, Montpellier, France
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- Dirk Schuebeler
- Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland
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- Tom Owen-Hughes
- Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, United Kingdom
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- Sylvain Daujat
- Department of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR, Strasbourg, France
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- Robert Schneider
- Department of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR, Strasbourg, France
説明
<jats:p>Post-translational modifications of proteins have emerged as a major mechanism for regulating gene expression. However, our understanding of how histone modifications directly affect chromatin function remains limited. In this study, we investigate acetylation of histone H3 at lysine 64 (H3K64ac), a previously uncharacterized acetylation on the lateral surface of the histone octamer. We show that H3K64ac regulates nucleosome stability and facilitates nucleosome eviction and hence gene expression in vivo. In line with this, we demonstrate that H3K64ac is enriched in vivo at the transcriptional start sites of active genes and it defines transcriptionally active chromatin. Moreover, we find that the p300 co-activator acetylates H3K64, and consistent with a transcriptional activation function, H3K64ac opposes its repressive counterpart H3K64me3. Our findings reveal an important role for a histone modification within the nucleosome core as a regulator of chromatin function and they demonstrate that lateral surface modifications can define functionally opposing chromatin states.</jats:p>
収録刊行物
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- eLife
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eLife 3 e01632-, 2014-03-25
eLife Sciences Publications, Ltd