[BMAL1 and circadian rhythm].

hBmal1 cDNA has been cloned from a human brain cDNA library and revealed that the cDNA encoded a novel bHLH-PAS transcription factor. The rBmal1 mRNA expression was found not only at high levels in the suprachiasmatic nuclei (SCN), but also in the pyriform cortex, hippocampus, and cerebellum. Furthermore, this expression was found in the eyes, pineal body, and peripheral organs, such as the muscle, liver, and heart. Bmal1 mRNA levels reveal a circadian rhythm in the rat SCN, with the highest expression levels at ZT18. The yeast two-hybrid screening have demonstrated that CLOCK forms a heterodimer with BMAL1. CLOCK. BMAL1 heterodimer functions as a positive transcription factor through binding to the E-box in the promoter region of the mPer1. Nuclear translocation is promoted by dimerization among PERs, or between PERs and CRYs, and the complexes inhibit the transcription of their own genes. This feedback loop is used in the clock output system driving the transcription of arginine vasopressin peptide and serotonin N-acetyl-transferase by binding the CLOCK-BMAL1 dimer to an E-box in their promoters.