Involvement of CLOCK:BMAL1 heterodimer in serum-responsive mPer1 induction.
A rapid induction of mouse period1 (mPer1) gene expression is supposed to be critical in the clock gene regulation, especially in the phase resetting of the clock, but its molecular mechanism is poorly understood. Based on the previous finding that the process does not involve de novo synthesis of proteins, we postulated the involvement of CLOCK:BMAL1 heterodimer, a positive regulator of circadian oscillator, in the rapid induction of mPer1 transcription. To test this hypothesis, we utilized CLOCKdelta19, a dominant-negative mutant, to suppress the function of CLOCK:BMAL1 in vitro. Serum-evoked rapid increases of mPer1 mRNA expression and promoter activity were significantly blunted when CLOCK:BMAL1 function was interfered with. Furthermore, DNA binding activity of CLOCK:BMAL1 heterodimer to five E-boxes of mPer1 promoter markedly increased shortly after serum shock. Taken together, these results suggest that CLOCK:BMAL1 heterodimer is not only a core component of negative feedback loop driving circadian oscillator, but also involved in the rapid induction of mPer1during phase resetting of the clock.
Jung
Hosung
H
Development and Neuroendocrine Research Laboratory, School of Biomedical Sciences, Seoul National University, Korea.
Choe
Youngshik
Y
Kim
Hyunjung
H
Park
Noheon
N
Son
Gi Hoon
GH
Khang
Inkoo
I
Kim
Kyungjin
K
D016475:3T3 Cells / Q000187:drug effects; D056930:ARNTL Transcription Factors; D000483:Alleles; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D002417:Cattle; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D025461:Feedback, Physiological; D005312:Fetal Blood / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D005799:Genes, Dominant; D017930:Genes, Reporter; D016762:Genes, fos; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D056950:Period Circadian Proteins; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D014162:Transfection
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D004247:DNA; D008156:Luciferases; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C538961:Bmal1 protein, mouse; C539023:Per1 protein, mouse; C538944:Clock protein, mouse