Research Article Differential regulation of the Sir2 histone deacetylase gene family by inhibitors of class I and II histone deacetylases

The Sir2 histone deacetylase gene family con- sists of seven mammalian sirtuins (SIRTs) which are NAD-dependent histone/protein deacetylases. Sir2 pro- teins regulate, for instance, genome stability by chro- matin silencing in yeast. In mammals, their function is still largely unknown. Due to the NAD + dependency, Sir2 might be the link between metabolic activity and his- tone/protein acetylation. Regulation of gene expression also seems to play an important role in Sir2 functions, since increasing the dosage of Sir2 genes increases genome stability in yeast and Caenorhabditis elegans. We observed that the modification of histone/protein acetylation status by several class I and II histone deacetylase (HDAC) inhibitors induces differential changes in gene expression profiles of seven SIRT mR- NAs in cultured neuronal cells. SIRT2, SIRT4 and SIRT7 were upregulated, whereas SIRT1, SIRT5 and SIRT6