Transcriptional oscillation of canonical clock genes in mouse peripheral tissues.
BACKGROUND
The circadian rhythm of about 24 hours is a fundamental physiological function observed in almost all organisms from prokaryotes to humans. Identification of clock genes has allowed us to study the molecular bases for circadian behaviors and temporal physiological processes such as hormonal secretion, and has prompted the idea that molecular clocks reside not only in a central pacemaker, the suprachiasmatic nuclei (SCN) of hypothalamus in mammals, but also in peripheral tissues, even in immortalized cells. Furthermore, previous molecular dissection revealed that the mechanism of circadian oscillation at a molecular level is based on transcriptional regulation of clock and clock-controlled genes.


RESULTS
We systematically analyzed the mRNA expression of clock and clock-controlled genes in mouse peripheral tissues. Eight genes (mBmal1, mNpas2, mRev-erbalpha, mDbp, mRev-erbbeta, mPer3, mPer1 and mPer2; given in the temporal order of the rhythm peak) showed robust circadian expressions of mRNAs in all tissues except testis, suggesting that these genes are core molecules of the molecular biological clock. The bioinformatics analysis revealed that these genes have one or a combination of 3 transcriptional elements (RORE, DBPE, and E-box), which are conserved among human, mouse, and rat genome sequences, and indicated that these 3 elements may be responsible for the biological timing of expression of canonical clock genes.


CONCLUSIONS
The observation of oscillatory profiles of canonical clock genes is not only useful for physiological and pathological examination of the circadian clock in various organs but also important for systematic understanding of transcriptional regulation on a genome-wide basis. Our finding of the oscillatory expression of canonical clock genes with a temporal order provides us an interesting hypothesis, that cyclic timing of all clock and clock-controlled genes may be dependent on several transcriptional elements including 3 known elements, E-box, RORE, and DBPE.
Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan. Takuro.Yamamoto@jp.sony.com <Takuro.Yamamoto@jp.sony.com>
Takuro
T
Yamamoto
Yasukazu
Y
Nakahata
Haruhiko
H
Soma
Makoto
M
Akashi
Takayoshi
T
Mamine
Toru
T
Takumi
D056930:ARNTL Transcription Factors; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D009928:Organ Specificity / Q000235:genetics; D056950:Period Circadian Proteins; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D056950:Period Circadian Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C538960:BMAL1 protein, human; C538961:Bmal1 protein, mouse; C485975:DBP protein, rat; C498260:Dbp protein, mouse; C491259:Npas2 protein, mouse; C498262:Nr1d1 protein, mouse; C539022:PER1 protein, human; C421902:PER2 protein, human; C512644:PER3 protein, human; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; C513312:Per2 protein, mouse; C513311:Per2 protein, rat; C512645:Per3 protein, mouse; C512646:Per3 protein, rat