Role of cyclic mPer2 expression in the mammalian cellular clock.
To explore the role of mPer2 in the circadian oscillation in the mammalian cellular clock, we established fibroblast cell lines in which expression of mPer2 is controlled through a tetracycline-regulatable promoter. We revealed that constitutive expression and overexpression of mPer2 mRNA severely impair serum shock-induced cyclic circadian clock gene expression. Moreover, under conditions of lower mPer2 mRNA expression, mPER2 protein accumulation in these cells showed clear circadian oscillation even in constitutive mPer2 mRNA expression, suggesting that the protein cycling of mPER2 was required for oscillation of the circadian feedback loop. Since the rhythms of gene expression driven by the intrinsic clock oscillation system dampen rapidly in the absence of cyclic expression of mPer2, the transcriptional rhythm helps to sustain the clock oscillation.
Yamamoto
Yoshinobu
Y
Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Yagita
Kazuhiro
K
Okamura
Hitoshi
H
D000818:Animals; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D003470:Culture Media; D004318:Doxycycline / Q000494:pharmacology; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D056950:Period Circadian Proteins; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014157:Transcription Factors; D025801:Ubiquitin / Q000378:metabolism
D018797:Cell Cycle Proteins; D003470:Culture Media; D009687:Nuclear Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D004318:Doxycycline