From the Guidelines
Clock genes, including CLOCK, BMAL1, PER, and CRY, are the primary regulators of the body's circadian rhythms, controlling the internal 24-hour cycles that govern various biological processes, such as sleep-wake cycles, hormone production, and metabolism. These genes work together in a transcription-translation feedback loop, inducing and suppressing each other's activity to maintain the circadian clock system, as described in a 2020 study published in the Annual Review of Public Health 1. The circadian rhythm process relies on the expression of these clock genes, which in turn controls the time-dependent expression profile of multiple genes and messengers/hormones in a 24-h rhythm. Disruption of the circadian clock, such as that caused by sleep deprivation or around-the-clock noise, can have severe consequences, including inflammatory conditions, endothelial dysfunction, and increased risk of diabetes and heart disease, as supported by human data on the adverse effects of sleep restriction on insulin sensitivity and the risk of diabetes 1.
Some of the key clock genes include:
- CLOCK: a transcriptional activator that induces the expression of PER and CRY
- BMAL1: a transcriptional activator that works with CLOCK to induce PER and CRY expression
- PER: a gene that is induced by the CLOCK/BMAL complex and suppresses the activity of the CLOCK/BMAL complex
- CRY: a gene that is induced by the CLOCK/BMAL complex and suppresses the activity of the CLOCK/BMAL complex
The circadian clock system regulates and controls various fundamental processes, including inflammation via the NF-κB pathway, DNA repair proteins and antioxidant defense, stress hormone levels, and other endocrine factors, highlighting the importance of clock genes in maintaining overall health and preventing disease, as discussed in the 2020 study 1.
From the Research
Definition of Clock Genes
Clock genes, also known as circadian rhythm genes, are a set of genes that regulate the biological clock and are responsible for controlling various physiological and behavioral processes, including feeding behavior and energy metabolism 2, 3, 4, 5, 6.
Key Clock Genes
Some of the key clock genes include:
- BMAL1 and CLOCK (positive regulators) 2
- CRY1, CRY2, PER1, PER2, and PER3 (negative regulators) 2 These genes are highly conserved during evolution and are found in insects as well as mammals 5.
Function of Clock Genes
The clock genes are organized in a system of interlocked transcriptional feedback loops, which generate 24-h molecular oscillations 3, 5. The period of the molecular oscillations relies on the accumulation rate of the repressors, their transfer into the cell nucleus, their ability to inhibit transcription, and their lifetime 5.
Importance of Clock Genes
The clock genes play a crucial role in regulating various physiological processes, including:
Dysregulation of Clock Genes
Dysregulation of clock genes has been associated with various diseases, including: