Per1

PER1, short for Period circadian regulator 1, is a gene that encodes a core component of the mammalian circadian clock. It is one of three PERIOD genes in humans and other mammals (PER1, PER2, PER3) that participate in a transcription-translation feedback loop responsible for approximately 24-hour rhythms. PER1 is expressed in the central clock, the suprachiasmatic nucleus (SCN), as well as in peripheral tissues.

In the molecular clock, CLOCK and BMAL1 activate the transcription of Per1 and other clock genes. The PER1 protein, along with CRY proteins, accumulates in the cytoplasm, forms a repressive complex, and moves into the nucleus to inhibit CLOCK-BMAL1-driven transcription. This negative feedback reduces its own expression, allowing the cycle to restart as PER1 is degraded. The stability and timing of PER1 are modulated by phosphorylation, notably by casein kinase 1 delta and epsilon (CK1δ/ε), which influence the period length of the clock.

Light input to the circadian system resets the clock in part by inducing Per1 transcription in the SCN through retinal signaling and CREB-mediated pathways. PER1 rhythms are present in the SCN and in many peripheral tissues, where daily fluctuations in mRNA and protein levels persist in a cell-autonomous manner.

Genetic alterations in PER1 can affect circadian timing and are studied in relation to sleep disorders such as familial advanced sleep phase syndrome. Polymorphisms in PER1 have also been examined for associations with diurnal preference. Beyond timekeeping, PER1 is explored for potential links to broader cellular processes, including cell cycle regulation and DNA damage response, reflecting the broader integration of circadian biology with cellular physiology.