title: Nuclear respiratory factor 2 induces SIRT3 expression.
abstract: The mitochondrial deacetylase SIRT3 regulates several important metabolic processes. SIRT3 is transcriptionally upregulated in multiple tissues during nutrient stresses such as dietary restriction and fasting, but the molecular mechanism of this induction is unclear. We conducted a bioinformatic study to identify transcription factor(s) involved in SIRT3 induction. Our analysis identified an enrichment of binding sites for nuclear respiratory factor 2 (NRF-2), a transcription factor known to play a role in the expression of mitochondrial genes, in the DNA sequences of SIRT3 and genes with closely correlated expression patterns. In vitro, knockdown or overexpression of NRF-2 modulated SIRT3 levels, and the NRF-2α subunit directly bound to the SIRT3 promoter. Our results suggest that NRF-2 is a regulator of SIRT3 expression and may shed light on how SIRT3 is upregulated during nutrient stress.
authors.affiliation: Harvard School of Engineering and Applied Sciences, Cambridge, MA, 02138, USA.|Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: F Kyle
authors.initials: FK
authors.lastname: Satterstrom
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Swindell
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Laurent
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Sejal
authors.initials: S
authors.lastname: Vyas
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.|Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Bulyk
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Marcia C
authors.initials: MC
authors.lastname: Haigis
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D019295:Computational Biology; D004790:Enzyme Induction / Q000235:genetics; D051268:GA-Binding Protein Transcription Factor / Q000172:deficiency / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D056566:Sirtuin 3 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D051268:GA-Binding Protein Transcription Factor; C466093:SIRT3 protein, human; D056566:Sirtuin 3
keywords: SIRT3; calorie restriction; dietary restriction; microarray analysis; nuclear respiratory factor 2