Exploring CLOCK: Our Inner Timekeeper


Our cells contain tiny molecular clocks that control a multitude of physiological and behavioral processes according to the circadian rhythm. Governed by a central clock, residing in the suprachiasmic nucleus of the brain, peripheral clocks are present in almost all tissues and organs (Hastings et al., 2003). They are, though able to persist in the absence of environmental cues, driven by the 24-hour patterns of light and temperature produced by the earth´s rotation, and periodically regulate functions such as body temperature, blood pressure, circulating hormones and metabolism (Mazzoccoli et al., 2012).

A major component of these molecular clocks is the CLOCK protein. Along with its heterodimeric partner BMAL1 (Brain and Muscle ARNT-like 1), it forms a transcriptional activator complex that rhythmically binds to specific DNA sequences, particularly E-box elements, in the promoters of target genes (Buhr, 2013). Naturally, it localizes mainly to the nucleoplasm, as shown in U251MG cells in this image, but has also been found in vesicles (Thul et al., 2017). To date, NCBI reports CLOCK to have experimentally confirmed interactions with over 80 genes, involved in everything from lipid and glucose metabolism to sleep regulation and blood pressure. It also initiates transcription of other core clock genes, such as Period (Per) and Cryptochrome (Cry) which encode proteins that constitute the negative feedback loop of the circadian clock and repress its activity. To further enhance its ability to modulate the activity of its target genes, CLOCK possesses intrinsic acetyltransferase activity, allowing it to modify histones and other proteins involved in chromatin remodeling (Doi et al., 2006).

Dysregulation of CLOCK-mediated processes has been implicated in circadian rhythm disorders and associated ailments, such as sleep, metabolic, and mood pathologies. This emphasizes the critical role of CLOCK in maintaining our overall health and well-being.