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The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1 alpha
- Zhong, Lei (author)
- D'Urso, Agustina (author)
- Toiber, Debra (author)
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- Sebastian, Carlos (author)
- Henry, Ryan E. (author)
- Vadysirisack, Douangsone D. (author)
- Guimaraes, Alexander (author)
- Marinelli, Brett (author)
- Nir, Tomer (author)
- Clish, Clary B. (author)
- Vaitheesvaran, Bhavapriya (author)
- Iliopoulos, Othon (author)
- Kurland, Irwin (author)
- Dor, Yuval (author)
- Weissleder, Ralph (author)
- Shirihai, Orian S. (author)
- Ellisen, Leif W. (author)
- Espinosa, Joaquin M. (author)
- Mostoslavsky, Raul (author)
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- (creator_code:org_t)
- Elsevier BV, 2010
- 2010
- English.
- In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 140:2, s. 280-293
- Journal article (peer-reviewed)
Abstract
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- SIRT6 is a member of a highly conserved family of NAD(+)-dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6-deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the expression of multiple glycolytic genes. Specifically, SIRT6 appears to function as a corepressor of the transcription factor Hif1 alpha, a critical regulator of nutrient stress responses. Consistent with this notion, SIRT6-deficient cells exhibit increased Hif1 alpha activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration. Our studies uncover a role for the chromatin factor SIRT6 as a master regulator of glucose homeostasis and may provide the basis for novel therapeutic approaches against metabolic diseases, such as diabetes and obesity.
Keyword
- NATURAL SCIENCES
- NATURVETENSKAP
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- Stockholm University
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