Circadian gene expression is resilient to large fluctuations in overall transcription rates.
Mammalian circadian oscillators are considered to rely on transcription/translation feedback loops in clock gene expression. The major and essential loop involves the autorepression of cryptochrome (Cry1, Cry2) and period (Per1, Per2) genes. The rhythm-generating circuitry is functional in most cell types, including cultured fibroblasts. Using this system, we show that significant reduction in RNA polymerase II-dependent transcription did not abolish circadian oscillations, but surprisingly accelerated them. A similar period shortening was observed at reduced incubation temperatures in wild-type mouse fibroblasts, but not in cells lacking Per1. Our data suggest that mammalian circadian oscillators are resilient to large fluctuations in general transcription rates and temperature, and that PER1 has an important function in transcription and temperature compensation.
Dibner
Charna
C
Department of Molecular Biology & NCCR Frontiers in Genetics, University of Geneva, Geneva, Switzerland.
Sage
Daniel
D
Unser
Michael
M
Bauer
Christoph
C
d'Eysmond
Thomas
T
Naef
Felix
F
Schibler
Ueli
U
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D056931:Cryptochromes; D025461:Feedback, Physiological; D005420:Flavoproteins / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056950:Period Circadian Proteins; D012319:RNA Polymerase II / Q000378:metabolism; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; D005420:Flavoproteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors; D012319:RNA Polymerase II