| First Author | Asher G | Year | 2008 |
| Journal | Cell | Volume | 134 |
| Issue | 2 | Pages | 317-28 |
| PubMed ID | 18662546 | Mgi Jnum | J:139296 |
| Mgi Id | MGI:3807721 | Doi | 10.1016/j.cell.2008.06.050 |
| Citation | Asher G, et al. (2008) SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134(2):317-28 |
| abstractText | The mammalian circadian timing system is composed of a central pacemaker in the suprachiasmatic nucleus of the brain that synchronizes countless subsidiary oscillators in peripheral tissues. The rhythm-generating mechanism is thought to rely on a feedback loop involving positively and negatively acting transcription factors. BMAL1 and CLOCK activate the expression of Period (Per) and Cryptochrome (Cry) genes, and once PER and CRY proteins accumulate to a critical level they form complexes with BMAL1-CLOCK heterodimers and thereby repress the transcription of their own genes. Here, we show that SIRT1, an NAD(+)-dependent protein deacetylase, is required for high-magnitude circadian transcription of several core clock genes, including Bmal1, Rorgamma, Per2, and Cry1. SIRT1 binds CLOCK-BMAL1 in a circadian manner and promotes the deacetylation and degradation of PER2. Given the NAD(+) dependence of SIRT1 deacetylase activity, it is likely that SIRT1 connects cellular metabolism to the circadian core clockwork circuitry. |
