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p53 regulates Period2 expression and the circadian clock

Author

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  • Takao Miki

    (Medical School, University of Texas Health Science Center-Houston
    Present address: Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan)

  • Tomoko Matsumoto

    (Medical School, University of Texas Health Science Center-Houston)

  • Zhaoyang Zhao

    (Medical School, University of Texas Health Science Center-Houston)

  • Cheng Chi Lee

    (Medical School, University of Texas Health Science Center-Houston)

Abstract

The mechanistic interconnectivity between circadian regulation and the genotoxic stress response remains poorly understood. Here we show that the expression of Period 2 (Per2), a circadian regulator, is directly regulated by p53 binding to a response element in the Per2 promoter. This p53 response element is evolutionarily conserved and overlaps with the E-Box element critical for BMAL1/CLOCK binding and its transcriptional activation of Per2 expression. Our studies reveal that p53 blocks BMAL1/CLOCK binding to the Per2 promoter, leading to repression of Per2 expression. In the suprachiasmatic nucleus (SCN), p53 expression and its binding to the Per2 promoter are under circadian control. Per2 expression in the SCN is altered by p53 deficiency or stabilization of p53 by Nutlin-3. Behaviourally, p53−/− mice have a shorter period length that lacks stability, and they exhibit impaired photo-entrainment to a light pulse under a free-running state. Our studies demonstrate that p53 modulates mouse circadian behaviour.

Suggested Citation

  • Takao Miki & Tomoko Matsumoto & Zhaoyang Zhao & Cheng Chi Lee, 2013. "p53 regulates Period2 expression and the circadian clock," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3444
    DOI: 10.1038/ncomms3444
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    Cited by:

    1. Rukeia El-Athman & Nikolai N Genov & Jeannine Mazuch & Kaiyang Zhang & Yong Yu & Luise Fuhr & Mónica Abreu & Yin Li & Thomas Wallach & Achim Kramer & Clemens A Schmitt & Angela Relógio, 2017. "The Ink4a/Arf locus operates as a regulator of the circadian clock modulating RAS activity," PLOS Biology, Public Library of Science, vol. 15(12), pages 1-34, December.

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