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cAMP response element induces Per1 in vivo.

Keisuke Ikegami1, Masato Nakajima1, Yoichi Minami1

  • 1Department of Anatomy and Neurobiology, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.

Biochemical and Biophysical Research Communications
|August 19, 2020
PubMed
Summary

Light resets the circadian clock by influencing Per1 and Per2 gene expression in the brain. A specific cAMP-responsive element (CRE) in the Per1 gene promoter is crucial for this light-induced expression, while a CRE in the Per2 gene is not.

Keywords:
Circadian clockEntrainmentPhase response curveSuperchiasmatic nuclei

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Area of Science:

  • Chronobiology
  • Molecular Biology
  • Neuroscience

Background:

  • Light is a primary environmental cue for synchronizing the internal circadian clock with the external environment.
  • In mammals, light signals are transmitted to the suprachiasmatic nuclei (SCN), the master circadian pacemaker.
  • The cAMP response element (CRE) and CRE binding protein (CREB) pathway are implicated in mediating light-induced Per1 and Per2 gene expression in the SCN.

Purpose of the Study:

  • To investigate the functional role of specific cAMP-responsive elements (CREs) in the light-induced expression of Per1 and Per2 genes in the SCN.
  • To determine whether identified CREs are essential for mediating circadian rhythm phase shifts in response to light.

Main Methods:

  • Generation of genetically modified mice with deleted CRE sites in the Per1 and Per2 promoter regions.
  • Analysis of Per1 and Per2 gene expression in the SCN following light exposure at night.
  • Observation of behavioral rhythms under various light conditions in CRE-deleted mice.

Main Results:

  • Deletion of a cAMP-responsive CRE in the Per1 promoter significantly blunted light-induced Per1 expression in the SCN.
  • Deletion of an ATF4-associated CRE in the Per2 promoter did not affect light-induced Per2 expression.
  • Circadian behavioral rhythms under certain light conditions remained unaffected despite the attenuated Per1 induction.

Conclusions:

  • The cAMP-responsive CRE in the Per1 promoter is critical for light-induced Per1 expression in the SCN.
  • The ATF4-associated CRE in the Per2 promoter does not appear to mediate light-induced Per2 expression.
  • While Per1 induction is affected by CRE deletion, circadian entrainment to light may rely on other pathways or exhibit robustness under specific conditions.