The circadian E-box: when perfect is not good enough.

Life on earth has evolved on a photic carousel, spinning through alternating periods of light and darkness. This playful image belies the fact that only those organisms that learned how to benefit from the recurring features in their environment were allowed to ride on. This selection process has engendered many daily rhythms in our biosphere, most of which rely on the anticipatory power of an endogenously generated marker of phase: the biological clock. The basic mechanisms driving this remarkable device have been really tough to decode but are finally beginning to unravel as chronobiologists probe deeper and wider in and around the recently discovered gears of the clock. Like its chemical predecessors, biological circadian oscillators are characterized by interlaced positive and negative feedback loops, but with constants and variables carefully balanced to achieve an approximately 24h period. The loops at the heart of these biological oscillators are sustained by specific patterns of gene expression and precisely tuned posttranscriptional modifications. It follows that a molecular understanding of the biological clock hinges, in no small measure, on a better understanding of the cis-acting elements that bestow a given gene with its circadian properties. The present review summarizes what is known about these elements and what remains to be elucidated.