Clockgenerna

Clockgenerna, or clock genes, are a set of genes that generate and regulate circadian rhythms—intrinsic 24-hour cycles that coordinate daily physiology and behavior. In mammals, the core clock machinery centers on the transcription factors CLOCK and BMAL1 (ARNTL), which form a heterodimer that activates the transcription of Period (PER1–PER3) and Cryptochrome (CRY1–CRY2) genes. The PER and CRY proteins accumulate, form complexes, and inhibit CLOCK-BMAL1 activity, creating a negative feedback loop that generates oscillations in gene expression.

Additional components refine and stabilize the clock. REV-ERBα/β and the ROR family regulate the transcription of Bmal1, linking the core loop to broader metabolic cues. Post-translational regulation by kinases such as CK1ε/δ, CK2, and GSK3β controls the stability and timing of PER and CRY proteins. Other clock-controlled genes participate in auxiliary feedback loops that help maintain precision and provide outputs that drive daily rhythms in physiology.

The central clock resides in the suprachiasmatic nucleus of the hypothalamus, which synchronizes the organism to the light-dark cycle. Light information is conveyed to the clock, allowing entrainment. Peripheral clocks exist in nearly all tissues and can be entrained by cues like feeding and temperature, enabling tissue-specific rhythms while remaining coordinated with the central clock.

Clockgenerna are highly conserved across species and regulate processes such as sleep-wake cycles, metabolism, hormone release, and immune function. Disruptions can be associated with sleep disorders, metabolic syndrome, and mood disorders, making chronobiology an active field of research and clinical interest.