SIRT1 regulates circadian clock gene expression through PER2 deacetylation.

Détails

ID Serval
serval:BIB_EBC480770821
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
SIRT1 regulates circadian clock gene expression through PER2 deacetylation.
Périodique
Cell
Auteur(s)
Asher G., Gatfield D., Stratmann M., Reinke H., Dibner C., Kreppel F., Mostoslavsky R., Alt F.W., Schibler U.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Statut éditorial
Publié
Date de publication
2008
Volume
134
Numéro
2
Pages
317-328
Langue
anglais
Résumé
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.
Mots-clé
ARNTL Transcription Factors, Acetylation, Animals, Basic Helix-Loop-Helix Transcription Factors/metabolism, CLOCK Proteins, Cell Cycle Proteins/metabolism, Cells, Cultured, Circadian Rhythm, Embryo, Mammalian/cytology, Fibroblasts/metabolism, Gene Expression Regulation, Liver/metabolism, Mice, NIH 3T3 Cells, Nuclear Proteins/metabolism, Period Circadian Proteins, Sirtuin 1, Sirtuins/metabolism, Trans-Activators/metabolism, Transcription Factors/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/12/2012 12:24
Dernière modification de la notice
20/08/2019 17:13
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