The 5 ' upstream region of mPer1 gene contains two promoters and is responsible for circadian oscillation

The mPer1 gene is assumed to be a key molecule in the regulation and functi oning of the mammalian circadian clock, which is based on the oscillation g enerated by a transcription-(post)translation feedback loop of a set of clo ck genes [1]. Robust circadian oscillation and acute light-elicited inducti on of mPer1 mRNA expression have been observed in the suprachiasmatic nucle us (SCN), the mammalian circadian center [2,3]. To Investigate the mechanis m underlying the complex regulation of mPer1 expression, we isolated and ch aracterized the 5' upstream region of the mPer1 gene. Unexpectedly, we iden tified two promoters, each followed by alternative first exons of mPer1, Co nsistent with the presence of multiple E-boxes in the promoters, exon-speci fic in site hybridization of the SCN established that both promoters functi on in circadian oscillation and in light-induction of mPer1 expression. Tra nsgenic mice carrying the 5' upstream region of the mPer1 gene fused to the luciferase gene demonstrated that a DNA fragment carrying both promoter re gions is sufficient to elicit striking circadian oscillation in the SCN and responsiveness to light. Moreover, luminescence in the SCN accurately mirr ored the mPer1 transcriptional activity. These transgenic mice will be very useful for monitoring clock-specific mPer1 expression in intact organisms and to follow the circadian clock in real time.