Transcription regulation within the circadian clock: The E-box and beyond

The circadian oscillator is composed of transcriptional feedback loops in organisms ranging from cyanobacteria to humans. These transcriptional feedback loops are so named because transcriptional regulators accumulate to high levels and then feed back to control their own genes' transcription, thus generating a self-sustaining rhythm in gene expression. In insects and vertebrates, the genes that encode these feedback regulators are remarkably well conserved and function to control not 1 but 2 feedback loops. These feedback loops control rhythmic transcription in opposite phases of the circadian cycle, yet they are interlocked because they share a number of components. In this review, the author will compare transcriptional regulatory mechanisms within the Drosophila and mammalian feedback loops and outline remaining questions concerning transcriptional regulation within and downstream of these feedback loops.