Protein Involved in Regulating Body Clock
SIRT1 controls expression of circadian genes, interacts with an important regulator
FRIDAY, July 25 (HealthDay News) -- The SIRT1 protein is involved in regulating the body clock by controlling the expression of circadian genes and interacting with an important core regulator of the cellular circadian clock machinery, according to two studies in the July 25 issue of Cell.
In the first study, Yasukazu Nakahata, Ph.D., from the University of California-Irvine, and colleagues investigated the role of the histone deacetylase activity of the SIRT1 protein in controlling circadian rhythms in cultured cells and in mouse liver. This activity may counteract the histone acetyltransferase activity of the CLOCK protein, a core element of the circadian clock machinery, they hypothesized. They found that SIRT1 and CLOCK physically associated and regulated circadian gene expression, and inhibiting SIRT1 activity resulted in less stringent circadian gene expression. Using mice with a mutated Sirt1 gene in the liver, they also found that SIRT1 contributed to circadian control in vivo.
In the second study, Gad Asher, from the University of Geneva in Switzerland, and colleagues examined the role of the SIRT1 protein in controlling circadian gene expression. They found that SIRT1 was required for high expression of several core genes involved in circadian rhythms, bound a CLOCK protein complex in a circadian manner, and modified and degraded another important circadian protein.
"Given the NAD+ dependence of SIRT1 deacetylase activity, it is likely that SIRT1 connects cellular metabolism to the circadian core clockwork circuitry," Asher and colleagues conclude.