Sir2 encodes the Drosophila homolog of the class III histone/protein deacetylase (HDAC) Sir2/Sirt1 that is evolutionarily conserved from yeast to man, and it has been implicated in the regulation of gene expression, protein activity, lifespan, and, more recently, in circadian and cocaine behaviors (Furuyama et al., 2004; Nakahata et al., 2009; Ramsey et al., 2009; Renthal et al., 2009). Expression of Sir2 in fly heads was transiently reduced to about half of normal levels by ethanol exposure (Fig. 2E,F). Expression of Sir2 was also found to be decreased following 2 brief exposures to high concentration ethanol vapor (Morozova et al., 2006). Of the 4 other class III HDAC-encoding genes in flies, Sirt2 was also down-regulated by ethanol exposure in the microarray analysis. Additionally, the HDAC class I-encoding gene Rpd3 was up-regulated, but expression of other HDAC-encoding genes were unaffected by ethanol exposure (Table S1). A targeted deletion of Sir2, 2A-7–11, removes most of the Sir2 coding region without affecting the expression levels of the neighboring DnaJ-H gene (Fig. 7A,B). These Sir2 null mutant flies were fully viable and fertile, and
