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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

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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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Authors: Schmutz, I., Ripperger, J. A., Baeriswyl-Aebischer, S., & Albrecht, U.
Affiliations: University of Fribourg (CH)
ORCID: Schmutz, Isabelle
Ripperger, Jürgen A.
Albrecht, Urs
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 2010-02-15
Volume: 24
Issue: 4
Pages: 345-357
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.564110
PMC: PMC2816734
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: bronze
doi.org
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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The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors

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