Scientists around Tom Burris, The Scripps Research Institute, FL, USA, have identified a novel mechanism that regulates circadian rhythm, the master clock that controls the body’s natural 24-hour physiological cycle. The findings could provide a new target for jet lag, shift work, sleep disturbances, as well as disorders that result from circadian rhythm disruption, including diabetes, obesity and some types of cancer.
The mammalian clock is regulated at the cellular level by a transcriptional/translational feedback loop. The expression of the nuclear receptors RORá and REV-ERBá follows a 24-hour circadian pattern (with opposing phases) leading to the correct circadian pattern of gene expression of BMAL1 and NPAS2. BMAL1 and as discovered now NPAS2 are genes that encode proteins regulating circadian rhythm.
The scientists think it’s something of a competition between these two receptors for binding to promoters of these genes that triggers either the activation (RORá) or repression (REV-ERBá) of the gene.
- Characterization of the Core Mammalian Clock Component, NPAS2, as a REV-ERBá/RORá Target Gene
Christine Crumbley, Yongjun Wang, Douglas J. Kojetin, Thomas P. Burris
J. Biol. Chem. 2010, 285 (45).