Bioinformatic and molecular investigation of Sirt3 expression
© Satterstrom et al; licensee BioMed Central Ltd. 2012
Published: 1 June 2012
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.
Materials and 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.
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