Central circadian clock

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Central circadian clock

Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. This is achieved by ocular photoreception relaying signals to the suprachiasmatic nucleus (SCN) in the hypothalamus. Signals from the SCN cause the synchronization of independent circadian clocks throughout the body to appropriate phases. Signals that can entrain these peripheral clocks include humoral signals, metabolic factors, and body temperature

The circadian timekeeping mechanism adapts physiology to the 24-hour light/dark cycle. However, how the outputs of the circadian clock in different peripheral tissues communicate and synchronize each other is still not fully understood. The circadian clock has been implicated in the regulation of numerous processes, including metabolism, the cell cycle, cell differentiation, immune responses, redox homeostasis, and tissue repair. 

In mammals the suprachiasmatic nucleus (SCN) of the hypothalamus is the master circadian clock for the entire body. The SCN serves to synchronize the individual cells of the body to a uniform internal time more like the conductor of an orchestra rather than the generator of the tempo themselves. 

The molecular clock mechanism in mammals is currently understood as a transcriptional feedback loop involving at least ten genes. The genes Clock and Bmal1 (or Mop3) encode bHLH-PAS proteins that form the positive limb of the feedback circuit. The CLOCK:BMAL1 heterodimer initiates the transcription by binding to specific DNA elements, E-boxes (5′-CACGTG-3′) and E′-boxes (5′-CACGTT-3′) in the promoters of target genes. This set of activated genes includes members of the negative limb of the feedback loop including the Per (Per1 and, Per2) and Cry (Cry1 and Cry2) genes. Degradation of the negative limb proteins PER and CRY is required to terminate the repression phase and restart a new cycle of transcription. The stability/degradation rate of the PER and CRY proteins is key to setting the period of the clock.