transcriptional regulation appears to be fundamental to circadian oscillations of clock gene expression these oscillations are believed to control output rhythms the transcriptional feedback loop and a model of interlocked loops have been proposed as the basis for these oscillations we characterized the genomic structure of the mouse bmal1 gene mbmal1 and defined the mbmal1 promoter region transcription of mbmal1 was activated by cry1 cry2 and per2 and was repressed by bmal1 clock dimers therefore cry per2 and bmal1 clock play bidirectional roles in transcription when they are at high levels by late day and midnight respectively this underlies the opposite phase of bmal1 compared to cry and per we propose that a bmal1 negative feedback loop interlocks with the cry and per2 negative feedback loop by inter activation forming a third positive forward loop this transcriptional model suggests a molecular basis for the maintenance of stability persistence and period of circadian rhythms the transcriptional potency of cry is predominant within the mammalian clock suggesting a clearance mechanism for cry in period maintenance c 2002 elsevier science usa.