Molecular mechanisms of the biological clock in cultured fibroblasts.
In mammals, the central circadian pacemaker resides in the hypothalamic suprachiasmatic nucleus (SCN), but circadian oscillators also exist in peripheral tissues. Here, using wild-type and cryptochrome (mCry)-deficient cell lines derived from mCry mutant mice, we show that the peripheral oscillator in cultured fibroblasts is identical to the oscillator in the SCN in (i) temporal expression profiles of all known clock genes, (ii) the phase of the various mRNA rhythms (i.e., antiphase oscillation of Bmal1 and mPer genes), (iii) the delay between maximum mRNA levels and appearance of nuclear mPER1 and mPER2 protein, (iv) the inability to produce oscillations in the absence of functional mCry genes, and (v) the control of period length by mCRY proteins.
Yagita
K
K
Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan.
Tamanini
F
F
van Der Horst
G T
GT
Okamura
H
H
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks / Q000235:genetics*; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019332:Endothelin-1 / Q000494:pharmacology; D005136:Eye Proteins; D005347:Fibroblasts / Q000502:physiology*; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D017956:Photoreceptor Cells, Invertebrate; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019332:Endothelin-1; D005136:Eye Proteins; D005420:Flavoproteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators; D014157:Transcription Factors; C538961:Bmal1 protein, mouse; C485975:DBP protein, rat; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; C513312:Per2 protein, mouse; C513311:Per2 protein, rat; C512645:Per3 protein, mouse; C512646:Per3 protein, rat; C119828:cry protein, Drosophila; C538944:Clock protein, mouse; C538945:Clock protein, rat