Multiple signaling pathways elicit circadian gene expression in cultured Rat-1 fibroblasts.
In mammals, all overt circadian rhythms are thought to be coordinated by a central pacemaker residing in the hypothalamic suprachiasmatic nucleus (SCN) [1]. The phase of this pacemaker is entrained by photic cues via the retino-hypothalamic tract. Circadian clocks probably rely on a feedback loop in the expression of certain clock genes (reviewed in [2,3]). Surprisingly, however, such molecular oscillators are not only operative in pacemaker cells, such as SCN neurons, but also in many peripheral tissues and even in cell lines kept in vitro [4-7]. For example, a serum shock can induce circadian gene expression in cultured Rat-1 fibroblasts [5]. This treatment also results in a rapid surge of expression of the clock genes Per1 and Per2, similar to that observed in the SCNs of animals receiving a light pulse [8-10]. Serum induction of Per1 and Per2 transcription does not require ongoing protein synthesis [5] and must therefore be accomplished by direct signaling pathways. Here, we show that cAMP, protein kinase C, glucocorticoid hormones and Ca2+ can all trigger a transient surge of Per1 transcription and elicit rhythmic gene expression in Rat-1 cells. We thus suspect that the SCN pacemaker may exploit multiple chemical cues to synchronize peripheral oscillators in vivo.
Balsalobre
A
A
Département de Biologie Moléculaire, Sciences II, Université de Genève, Switzerland.
Marcacci
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L
Schibler
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U
D000818:Animals; D001683:Biological Clocks; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D018797:Cell Cycle Proteins; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics*; D005576:Colforsin / Q000494:pharmacology; D003470:Culture Media; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics*; D019319:Okadaic Acid / Q000494:pharmacology; D056950:Period Circadian Proteins; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects
D018797:Cell Cycle Proteins; D003470:Culture Media; D007328:Insulin; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; C513312:Per2 protein, mouse; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D014157:Transcription Factors; D005576:Colforsin; D019319:Okadaic Acid; D000001:Calcimycin; D004815:Epidermal Growth Factor; D003994:Bucladesine; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide