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Acetylation of BMAL1 by TIP60 controls BRD4-P-TEFb recruitment to circadian promoters

  1. Nikolai Petkau
  2. Harun Budak
  3. Xunlei Zhou
  4. Henrik Oster
  5. Gregor Eichele  Is a corresponding author
  1. Max Planck Institute for Biophysical Chemistry, Germany
Research Article
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Cite this article as: eLife 2019;8:e43235 doi: 10.7554/eLife.43235

Abstract

Many physiological processes exhibit circadian rhythms driven by cellular clocks composed of interlinked activating and repressing elements. To investigate temporal regulation in this molecular oscillator, we combined mouse genetic approaches and analyses of interactions of key circadian proteins with each other and with clock gene promoters. We show that transcriptional activators control BRD4-PTEFb recruitment to E-box-containing circadian promoters. During the activating phase of the circadian cycle, the lysine acetyltransferase TIP60 acetylates the transcriptional activator BMAL1 leading to recruitment of BRD4 and the pause release factor P-TEFb, followed by productive elongation of circadian transcripts. We propose that the control of BRD4-P-TEFb recruitment is a novel temporal checkpoint in the circadian clock cycle.

Article and author information

Author details

  1. Nikolai Petkau

    Department of Genes and Behavior, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9168-3473
  2. Harun Budak

    Department of Genes and Behavior, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7371-8959
  3. Xunlei Zhou

    Department of Genes and Behavior, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Henrik Oster

    Department of Genes and Behavior, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Gregor Eichele

    Department of Genes and Behavior, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    For correspondence
    gregor.eichele@mpibpc.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2863-9127

Funding

Volkswagen Foundation (Lichtenberg Fellowship)

  • Henrik Oster

Max-Planck-Gesellschaft (Open-access funding)

  • Gregor Eichele

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Mouse handling was carried out in accordance with the German Law on Animal Welfare and was ethically approved and licensed by the Office of Consumer Protection and Food Safety of the State of Lower Saxony (license numbers 33.11.42502-04/072/07 and 33.9-42502-04-12/0719).

Reviewing Editor

  1. Asifa Akhtar, Max Planck Institute for Immunobiology and Epigenetics, Germany

Publication history

  1. Received: November 1, 2018
  2. Accepted: July 10, 2019
  3. Accepted Manuscript published: July 11, 2019 (version 1)

Copyright

© 2019, Petkau et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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