A rhythmic Ror.

The circadian clock mechanism in mammals involves two interlocking transcriptional feedback loops. Rev-erb alpha, through its role as a transcriptional repressor, was thought to be the primary determinant of the feedback loop that regulates Bmal1 transcription. Results reported by Sato et al. in this issue of Neuron now show that the transactivator Rora acts coordinately with Rev-erb alpha and that their competing activities on the same promoter element drive the rhythm in Bmal1 transcription. This finding defines the second feedback loop in mammals.