Transcriptional oscillation of canonical clock genes in mouse peripheral tissues

We systematically analyzed the mRNA expression of clock and clock-controlled genes in mouse peripheral tissues. Eight genes (mBmal1, mNpas2, mRev-erbα, mDbp, mRev-erbβ, 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.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.The circadian rhythm of about 24 hours is a fundamental physiological function observed in almost all organisms from prokaryotes to humans. Circadian rhythms have been known to be generated in pacemaker cells, the suprachiasmatic nuclei (SCN) of hypothalamus in mammals, and entrained by environmental cues, such as light, temperature, noise, feeding or social cues, whereas a recent analysis using mPer2luciferase knockin mice has demonstrated that peripheral tissues express self-sustained circadian oscillations [1]. The output of circadian oscillation appears as locomotive activity, hormonal secretion, the sleep-wake cycle, and many other physiological functions. Disruption of the circadian rhythms has been as