Cell · 1995 · 359 citations · 24 references
Life SciencesBiologyMolecular BiologyCircadian RhythmsGene ExpressionGene RegulationCircadian Clock MechanismsCircadian Gene ExpressionCircadian Molecular MechanismsCircadian PhysiologyMolecular ClocksCircadian ClocksCircadian Light EntrainmentCircadian Regulation Of Gene ExpressionCircadian Transcriptional RegulationClock ResettingEntrainment MechanismsLight-entrained Gene ExpressionVisible Light Effects
The frequency (frq) gene is rapidly induced by brief light pulses, and this induction is essential for circadian clock resetting. The study examined how light entrains circadian clocks by investigating the effects of light on the frq gene. Light induction overcomes frq negative autoregulation, allowing frq expression to remain high in constant light. The rapid and robust induction of frq by light appears to be the initial clock‑specific event that converts a unidirectional light signal into bidirectional time‑of‑day advances and delays, and this model generalizes to explain how circadian feedback cycles synchronize with external cycles.
To understand how light entrains circadian clocks, we examined the effects of light on a gene known to encode a state variable of a circadian oscillator, the frequency (frq) gene. frq is rapidly induced by short pulses of visible light; clock resetting is correlated with frq induction and is blocked by drugs that block the synthesis of protein or translatable RNA. The speed and magnitude of frq induction suggest that this may be the initial clock-specific event in light resetting. Light induction overcomes frq negative autoregulation so that frq expression can remain high in constant light. These data explain how a simple unidirectional signal (light and the induction of frq) may be turned into a bidirectional clock response (time of day-specific advances and delays). This light entrainment model is easily generalized and may be the common mechanism by which the intracellular feedback cycles that comprise circadian clocks are brought into synchrony with external cycles in the real world.
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