Effect of nutrient deprivation on the expression and the epigenetic signature of sirtuin genes

Background and aim: Over the last decades advances in understanding the molecular bases of the close relationship between nutrition, metabolism, and diseases have been impres- sive. However, there are always novel frontiers coming up and epigenetics is one of these. Sir- tuins, are pivotal factors in the control of metabolic pathways according to nutrient availability. In the present study we evaluated the effect of nutrient deprivation on expression, DNA methylation and chromatin status of the sirtuin genes. Methods and results: We performed these studies in mouse hepatoma cells, that were grown in standard medium, or in media containing low glucose concentration, or no glucose, or no amino acids. We applied quantitative real-time PCR to cDNA, methylation-enriched DNA and nuclease- treated DNA in order to evaluate gene expression, DNA methylation, and chromatin condensa- tion, respectively. This study shows that the expression of sirtuin genes varies following nutrient deprivation. Moreover, we observed that changes of DNA methylation and chromatin condensa- tion occur at the transcription start site of sirtuin genes following nutrient deprivation. Conclusions: Epigenetic mechanisms may have a role in the sirtuin response to nutrient depriva- tions in cultured hepatoma cells. Replicating these results in vivo to achieve a comprehensive un- derstanding of the epigenetic control of sirtuin expression following nutrient deprivations might open up novel therapeutic possibilities to cure metabolic diseases and promote human health.