clockgene

Clock genes are a group of genes that regulate circadian rhythms in organisms ranging from bacteria to humans. They encode components of molecular clocks that create endogenous, approximately 24-hour cycles in physiology, behavior, and metabolism. The clock is highly conserved across species and coordinates daily cycles with environmental cues such as light.

At the core of most clocks is a transcription-translation feedback loop. In mammals, the CLOCK and BMAL1 proteins form a heterodimer that activates the transcription of Period (Per1, Per2, Per3) and Cryptochrome (Cry1, Cry2) genes by binding to E-box elements in their promoters. The PER and CRY proteins accumulate, form complexes, and eventually translocate back to the nucleus to inhibit CLOCK:BMAL1 activity, reducing their own transcription and allowing the cycle to reset. Additional regulatory layers include the REV-ERB and ROR families, which modulate BMAL1 expression, and post-translational modifications such as phosphorylation by casein kinase 1 to control protein stability and timing.

The master clock is located in the suprachiasmatic nucleus of the brain in mammals, but peripheral clocks exist in virtually all tissues and organs. Light information detected by the retina helps synchronize clocks to the external environment, ensuring alignment with day and night. Clock genes influence numerous processes, including sleep-wake cycles, hormone release, metabolism, and immune function.

Disruptions or mutations in clock genes can lead to circadian rhythm disorders and impact health. Research uses genetic knockouts, reporter gene systems, and chronotherapy approaches to study clock function and its implications for disease and well-being.