SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Export

@article{citeulike:3100977, abstract = {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.}, address = {Department of Molecular Biology, Sciences III, University of Geneva, 30, Quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland.}, author = {Asher, G. and Gatfield, D. and Stratmann, M. and Reinke, H. and Dibner, C. and Kreppel, F. and Mostoslavsky, R. and Alt, F. W. and Schibler, U.}, citeulike-article-id = {3100977}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cell.2008.06.050}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18662546}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18662546}, day = {25}, doi = {10.1016/j.cell.2008.06.050}, issn = {1097-4172}, journal = {Cell}, keywords = {circadian-clock, deacetylation, sirt1}, month = {July}, number = {2}, pages = {317--328}, posted-at = {2008-08-08 15:10:35}, priority = {2}, title = {SIRT1 regulates circadian clock gene expression through PER2 deacetylation.}, url = {http://dx.doi.org/10.1016/j.cell.2008.06.050}, volume = {134}, year = {2008} }

TY - JOUR ID - citeulike:3100977 L3 - citeulike-article-id:3100977 N2 - 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. IS - 2 JF - Cell SN - 1097-4172 AD - Department of Molecular Biology, Sciences III, University of Geneva, 30, Quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland. EP - 328 TI - SIRT1 regulates circadian clock gene expression through PER2 deacetylation. VL - 134 SP - 317 KW - circadian-clock KW - deacetylation KW - sirt1 AU - Asher, G AU - Gatfield, D AU - Stratmann, M AU - Reinke, H AU - Dibner, C AU - Kreppel, F AU - Mostoslavsky, R AU - Alt, FW AU - Schibler, U PY - 2008/07/25/ UR - http://dx.doi.org/10.1016/j.cell.2008.06.050 ER -