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

  • Schmutz, Isabelle Department of Medicine, Unit of Biochemistry, University of Fribourg, Switzerland
  • Ripperger, Jürgen A. Department of Medicine, Unit of Biochemistry, University of Fribourg, Switzerland
  • Baeriswyl-Aebischer, Stéphanie Department of Medicine, Unit of Biochemistry, University of Fribourg, Switzerland
  • Albrecht, Urs Department of Medicine, Unit of Biochemistry, University of Fribourg, Switzerland
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    2009
Published in:
  • Genes & Development. - 2010, vol. 24, p. 345-357
Circadian oscillator
transcription
protein–protein interaction
English 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 PPARα and REV-ERBα 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, Hnf1α, 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biological sciences
License
License undefined
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Persistent URL
https://folia.unifr.ch/unifr/documents/301502
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