Properties, entrainment, and physiological functions of mammalian peripheral oscillators.
In mammals, the circadian timing system is composed of multiple oscillators that are organized in a hierarchical manner. The central pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, is believed to orchestrate countless subsidiary clocks in the periphery. These peripheral oscillators are cell-autonomous, self-sustained, resilient to cell division, and virtually insensitive to large fluctuations in general transcription rates. However, they are probably not coupled within an organ, and daily zeitgeber signals emanating from the SCN appear to be required to ensure phase coherence within and between tissues. Peripheral clocks are implicated in a variety of biochemical pathways, and recent results tightly link circadian rhythms to several aspects of metabolism. Thus, the expression of many key enzymes conducting rate-limiting steps in various metabolic pathways is regulated in a circadian fashion by core clock components or clock-controlled transcription factors. Genetic loss-of-function studies have now established a role for mammalian circadian clock components in energy homeostasis and xenobiotic detoxification, and the latter manifests itself in the daytime-dependent modulation of drug efficacy and toxicity.
Stratmann
Markus
M
Department of Molecular Biology, National Center of Competence in Research Frontiers in Genetics, Sciences III, University of Geneva, Geneva, Switzerland.
Schibler
Ueli
U
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology; D001683:Biological Clocks / Q000502:physiology*; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins / Q000502:physiology; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology; D056950:Period Circadian Proteins; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D013696:Temperature; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D050976:Basic-Leucine Zipper Transcription Factors; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C538961:Bmal1 protein, mouse; C513312:Per2 protein, mouse; C538944:Clock protein, mouse