PreprintCited by 361Circadian rhythm and melatoninPlant Molecular Biology ResearchLight effects on plants

The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors

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Schmutz, Isabelle, Ripperger, Jürgen A., Baeriswyl-Aebischer, Stéphanie, Albrecht, Urs·2010·Genes & Development

Abstract

Mammalian circadian clocks provide a temporal framework to synchronize biological functions. To obtain robust rhythms with a periodicity of about a day, these clocks use molecular oscillators consisting of two interlocked feedback loops. The core loop generates rhythms by transcriptional repression via the Period (PER) and Cryptochrome (CRY) proteins, whereas the stabilizing loop establishes roughly antiphasic rhythms via nuclear receptors. Nuclear receptors also govern many pathways that affect metabolism and physiology. Here we show that the core loop component PER2 can coordinate circadian output with the circadian oscillator. PER2 interacts with nuclear receptors including PPARalpha and REV-ERBalpha and serves as a coregulator of nuclear receptor-mediated transcription. Consequently, PER2 is rhythmically bound at the promoters of nuclear receptor target genes in vivo. In this way, the circadian oscillator can modulate the expression of nuclear receptor target genes like Bmal1, Hnf1alpha, and Glucose-6-phosphatase. The concept that PER2 may propagate clock information to metabolic pathways via nuclear receptors adds an important facet to the clock-dependent regulation of biological networks.

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  • Per2 mutant mice show reduced fasting glycemia, loss of rhythmic glycogen accumulation in the liver, elevated plasma insulin levels and impaired gluconeogenesis.

    “Per2 mutant mice show reduced fasting glycemia, a loss of rhythmic glycogen accumulation in the liver, elevated plasma insulin levels and impaired gluconeogenesis [20–22]”

    From Circadian control of glucose metabolism (2014) · cites this paper as [20]

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Authors
Schmutz, I., Ripperger, J. A., Baeriswyl-Aebischer, S., & Albrecht, U.
Affiliations
University of Fribourg (CH)
Venue
Genes & Development
Published
2010-02-15
Volume
24
Issue
4
Pages
345-357
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2122503953
Cited by
361
References
64
Citations by year
2026: 6 · 2025: 22 · 2024: 12 · 2023: 17 · 2022: 19 · 2021: 26 · 2020: 14 · 2019: 21 · 2018: 14 · 2017: 21 · 2016: 23 · 2015: 23 · 2014: 37 · 2013: 30 · 2012: 35
Type
posted content
Language
en
Open access
Locations
  • Genes & Development (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • reroDoc Digital Library (submittedVersion)
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Light effects on plants
Keywords
Per2, circadian clock, nuclear receptors, PPARα, NR1D1, co-regulation, transcriptional repression, Bmal1, HNF1A, glucose-6-phosphatase, promoter binding
MeSH terms
Animals, Circadian Rhythm, Gene Expression Regulation, Glucose, Liver, Promoter Regions, Genetic, Protein Binding, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Amino Acid Motifs, NIH 3T3 Cells, PPAR alpha, Mice, ARNTL Transcription Factors, Period Circadian Proteins, Nuclear Receptor Subfamily 1, Group D, Member 1

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