- Poster presentation
- Open Access
Bioinformatic and molecular investigation of Sirt3 expression
© Satterstrom et al; licensee BioMed Central Ltd. 2012
- Published: 1 June 2012
- Calorie Restriction
- Fatty Acid Oxidation
- Zinc Finger Transcription Factor
- Similar Expression Profile
Fasting and calorie restriction cause significant metabolic changes as organisms try to maintain energy homeostasis. The mitochondrial NAD+-dependent protein deacetylase Sirt3 has important metabolic effects, including promotion of fatty acid oxidation during fasting  and repression of glycolysis in cancer cells . We sought to investigate the mechanisms by which Sirt3 is transcriptionally induced and regulated using both bioinformatic and molecular methods.
Our approach was two-pronged: using the DNA sequence analysis program PhylCRM , we analyzed the regulatory sequences of Sirt3 and genes with similar expression profiles to determine over-represented transcription factor binding sequences. We also conducted a quantitative real-time PCR-based targeted screen in HEK 293T cells to determine the effects of calorie restriction mimetic drugs on Sirt3 expression levels.
We have identified candidate transcription factors that may affect Sirt3 expression levels, including the zinc finger transcription factor MZF1. We have also analyzed the effect of several drugs on Sirt3 expression, notably observing a decrease in Sirt3 expression with resveratrol treatment.
We have identified transcription factors and calorie restriction mimetic drugs which may control Sirt3 expression and are currently conducting follow-up studies.
- Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard DB, Grueter CA, Harris C, Biddinger S, Ilkayeva OR, Stevens RD, Li Y, Saha AK, Ruderman NB, Bain JR, Newgard CB, Farese RV, Alt FW, Kahn CR, Verdin E: SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature. 2010, 464 (7285): 121-5.PubMed CentralPubMedView ArticleGoogle Scholar
- Finley LW, Carracedo A, Lee J, Souza A, Egia A, Zhang J, Teruya-Feldstein J, Moreira PI, Cardoso SM, Clish CB, Pandolfi PR, Haigis MC: SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization. Cancer Cell. 2011, 19 (3): 416-28.PubMed CentralPubMedView ArticleGoogle Scholar
- Warner JB, Philippakis AA, Jaeger SA, He FS, Lin J, Bulyk ML: Systematic identification of mammalian regulatory motifs’ target genes and functions. Nat Methods. 2008, 5 (4): 347-53.PubMed CentralPubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.