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Published on: September 27, 2012
p53 regulates Period2 expression and the circadian clock
Takao Miki1, Tomoko Matsumoto, Zhaoyang Zhao
11] Department of Biochemistry and Molecular Biology, Medical School, University of Texas Health Science Center-Houston, Houston, Texas 77030, USA [2].
Nature Communications
|September 21, 2013
Summary
The tumor suppressor p53 directly regulates the circadian clock gene Period 2 (Per2). This interaction impacts circadian rhythm stability and behavior in mice.
Area of Science:
- Molecular Biology
- Chronobiology
- Genetics
Background:
- The interplay between circadian rhythms and the genotoxic stress response is not well understood.
- Circadian regulators like Period 2 (Per2) are crucial for maintaining biological timing.
Purpose of the Study:
- To elucidate the mechanistic link between p53 and circadian gene regulation.
- To investigate the role of p53 in controlling Per2 expression and its impact on circadian behavior.
Main Methods:
- Analysis of p53 binding to the Per2 promoter.
- Investigating the effect of p53 on BMAL1/CLOCK binding to the Per2 promoter.
- Utilizing p53-deficient mice and Nutlin-3 treatment to assess Per2 expression and behavioral phenotypes.
Main Results:
- p53 directly binds to a conserved response element in the Per2 promoter, overlapping with the BMAL1/CLOCK binding site.
- p53 binding inhibits BMAL1/CLOCK from activating Per2 transcription.
- p53 deficiency or stabilization alters Per2 expression in the suprachiasmatic nucleus (SCN).
- p53-deficient mice exhibit unstable, shorter circadian periods and impaired light entrainment.
Conclusions:
- p53 acts as a repressor of Per2 expression by blocking transcriptional activators.
- p53 plays a significant role in modulating circadian rhythmicity and behavioral responses to environmental cues.
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