The Thymus Is Similar to the Testis in Its Pattern of Circadian Clock Gene Expression

Abstract

The molecular basis for the circadian clock in mammals consists of a number of genes and proteins that form transcription-translation feedback loops. These loops result in a 24-h rhythm in the expression of mRNA and protein levels. Although the anatomical site of the central circadian clock is the SCN of the hypothalamus, all of the circadian clock genes are expressed in tissues other than the brain. Moreover, cyclic gene and protein expression occurs in mostof these tissues. The best known exception to this rule is the testis, which shows constant rather than cyclic expression of circadian clock genes. Indeed, the testis of multiple animal species displays constant circadian clock gene expression. In recent work, the authors showed that the thymus is similar to the testis in that expression of circadian clock genes is either constant over a 24-h period or cycles with a dampened amplitude, depending on which gene is examined. In the current study, they extend and confirm their findings regarding noncyclic circadian clock gene and protein expression in the testis and the thymus. More important, they also show that expression of these genes in both testis and thymus does not depend on the transcriptional activator, CLOCK, which is necessary for cyclic gene expression in the SCN and in other tissues. These results extend the molecular similarities between the thymus and the testis and suggest that similar mechanisms are at work for regulating expression of circadian clock genes in both tissues. One commonality between these 2 organs is that they are composed primarily of differentiating cells. The authors hypothesize that the circadian clock is not operational in immature, differentiating cells. Possibly, the clock starts in mature cells upon receipt of an initiating signal.