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BMC Proceedings

Volume 6 Supplement 3

Metabolism, diet and disease

Open Access

Bioinformatic and molecular investigation of Sirt3 expression

  • F Kyle Satterstrom1, 2, 3,
  • William R Swindell4, 5,
  • Martha L Bulyk5, 6, 7 and
  • Marcia C Haigis2, 3
BMC Proceedings20126(Suppl 3):P40

https://doi.org/10.1186/1753-6561-6-S3-P40

Published: 1 June 2012

Background

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 [1] and repression of glycolysis in cancer cells [2]. We sought to investigate the mechanisms by which Sirt3 is transcriptionally induced and regulated using both bioinformatic and molecular methods.

Materials and methods

Our approach was two-pronged: using the DNA sequence analysis program PhylCRM [3], 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.

Results

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.

Conclusions

We have identified transcription factors and calorie restriction mimetic drugs which may control Sirt3 expression and are currently conducting follow-up studies.

Authors’ Affiliations

(1)
Harvard School of Engineering and Applied Sciences
(2)
Department of Cell Biology, Harvard Medical School
(3)
The Paul F. Glenn Labs for the Biological Mechanisms of Aging, Harvard Medical School
(4)
Department of Genetics, Harvard Medical School
(5)
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
(6)
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School
(7)
Division of Health Sciences and Technology, Harvard Medical School

References

  1. 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
  2. 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
  3. 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

Copyright

© Satterstrom et al; licensee BioMed Central Ltd. 2012

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.

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