title: Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators.
abstract: The circadian pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus maintains phase coherence in peripheral cells through metabolic, neuronal, and humoral signaling pathways. Here, we investigated the role of daily body temperature fluctuations as possible systemic cues in the resetting of peripheral oscillators. Using precise temperature devices in conjunction with real-time monitoring of the bioluminescence produced by circadian luciferase reporter genes, we showed that simulated body temperature cycles of mice and even humans, with daily temperature differences of only 3°C and 1°C, respectively, could gradually synchronize circadian gene expression in cultured fibroblasts. The time required for establishing the new steady-state phase depended on the reporter gene, but after a few days, the expression of each gene oscillated with a precise phase relative to that of the temperature cycles. Smooth temperature oscillations with a very small amplitude could synchronize fibroblast clocks over a wide temperature range, and such temperature rhythms were also capable of entraining gene expression cycles to periods significantly longer or shorter than 24 h. As revealed by genetic loss-of-function experiments, heat-shock factor 1 (HSF1), but not HSF2, was required for the efficient synchronization of fibroblast oscillators to simulated body temperature cycles.
authors.affiliation: Department of Molecular Biology, National Centers of Competence in Research Frontiers in Genetics, Sciences III, University of Geneva, CH-1211 Geneva-4, Switzerland.
authors.forename: Camille
authors.initials: C
authors.lastname: Saini
authors.forename: Jörg
authors.initials: J
authors.lastname: Morf
authors.forename: Markus
authors.initials: M
authors.lastname: Stratmann
authors.forename: Pascal
authors.initials: P
authors.lastname: Gos
authors.forename: Ueli
authors.initials: U
authors.lastname: Schibler
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000235:genetics / Q000502:physiology*; D057906:Circadian Clocks / Q000235:genetics / Q000502:physiology*; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D000076249:Heat Shock Transcription Factors; D008156:Luciferases / Q000235:genetics; D051379:Mice; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors; D008156:Luciferases