Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex.
The Sir2 histone deacetylases are important for gene regulation, metabolism, and longevity. A unique feature of these enzymes is their utilization of NAD(+) as a cosubstrate, which has led to the suggestion that Sir2 activity reflects the cellular energy state. We show that SIRT1, a mammalian Sir2 homologue, is also controlled at the transcriptional level through a mechanism that is specific for this isoform. Treatment with the glycolytic blocker 2-deoxyglucose (2-DG) decreases association of the redox sensor CtBP with HIC1, an inhibitor of SIRT1 transcription. We propose that the reduction in transcriptional repression mediated by HIC1, due to the decrease of CtBP binding, increases SIRT1 expression. This mechanism allows the specific regulation of SIRT1 in response to nutrient deprivation.
Zhang
Qinghong
Q
Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA. zhangq@ohsu.edu
Wang
Su-Yan
SY
Fleuriel
Capucine
C
Leprince
Dominique
D
Rocheleau
Jonathan V
JV
Piston
David W
DW
Goodman
Richard H
RH
D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003847:Deoxyglucose / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D053858:Metabolic Networks and Pathways; D051379:Mice; D009243:NAD / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
D004268:DNA-Binding Proteins; C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D009243:NAD; D003847:Deoxyglucose; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; C447939:SIRT1 protein, human; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins