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Brenna A, Ripperger JA, Saro G, et al. PER2 mediates CREB-dependent light induction of the clock gene Per1. Sci Rep. 2021;11(1):21766doi: 10.1038/s41598-021-01178-6.
Brenna, A., Ripperger, J. A., Saro, G., Glauser, D. A., Yang, Z., & Albrecht, U. (2021). PER2 mediates CREB-dependent light induction of the clock gene Per1. Scientific reports, 11(1), 21766. https://doi.org/10.1038/s41598-021-01178-6
Brenna, Andrea, et al. "PER2 mediates CREB-dependent light induction of the clock gene Per1." Scientific reports vol. 11,1 (2021): 21766. doi: https://doi.org/10.1038/s41598-021-01178-6
Brenna A, Ripperger JA, Saro G, Glauser DA, Yang Z, Albrecht U. PER2 mediates CREB-dependent light induction of the clock gene Per1. Sci Rep. 2021 Nov 05;11(1):21766. doi: 10.1038/s41598-021-01178-6. PMID: 34741086; PMCID: PMC8571357.
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Sci Rep. 2021 Nov 05;11(1):21766. doi: 10.1038/s41598-021-01178-6.

PER2 mediates CREB-dependent light induction of the clock gene Per1.

Scientific reports

Andrea Brenna, Jürgen A Ripperger, Gabriella Saro, Dominique A Glauser, Zhihong Yang, Urs Albrecht

Affiliations

  1. Department of Biology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
  2. Laboratory of Cardiovascular and Aging Research, Department of Endocrinology, Metabolism, Cardiovascular System, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
  3. Department of Biology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland. [email protected].

PMID: 34741086 PMCID: PMC8571357 DOI: 10.1038/s41598-021-01178-6

Abstract

Light affects many physiological processes in mammals such as entrainment of the circadian clock, regulation of mood, and relaxation of blood vessels. At the molecular level, a stimulus such as light initiates a cascade of kinases that phosphorylate CREB at various sites, including serine 133 (S133). This modification leads CREB to recruit the co-factor CRCT1 and the histone acetyltransferase CBP to stimulate the transcription of genes containing a CRE element in their promoters, such as Period 1 (Per1). However, the details of this pathway are poorly understood. Here we provide evidence that PER2 acts as a co-factor of CREB to facilitate the formation of a transactivation complex on the CRE element of the Per1 gene regulatory region in response to light or forskolin. Using in vitro and in vivo approaches, we show that PER2 modulates the interaction between CREB and its co-regulator CRTC1 to support complex formation only after a light or forskolin stimulus. Furthermore, the absence of PER2 abolished the interaction between the histone acetyltransferase CBP and CREB. This process was accompanied by a reduction of histone H3 acetylation and decreased recruitment of RNA Pol II to the Per1 gene. Collectively, our data show that PER2 supports the stimulus-dependent induction of the Per1 gene via modulation of the CREB/CRTC1/CBP complex.

© 2021. The Author(s).

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