1999; Garro et al. 1991; Hamid et al. 2009; Lu et al. 2000; Shukla et al. 2008). However, the effect of chronic alcohol on global DNA methylation seems to be tissue specific because one study reported enhanced DNA methylation (i.e., global DNA hypermethylation) in a certain type of blood cells (i.e., peripheral mononuclear cells) in alcoholic patients undergoing early alcohol withdrawal (Bonsch sellekchem et al. 2004). Two recent studies (Manzardo et al. 2012; Ponomarev et al. 2012) have examined alcohol��s effects on global DNA methylation in the brain. Both studies measured DNA methylation in the frontal cortex of chronic alcoholics and matched control cases, but using two different methods.

Ponomarev and colleagues (2012) studied genomic regions that included DNA sequences called long terminal repeat (LTR)-containing retrotransposons, also known as endogenous retroviruses (ERVs), most of which are nonfunctional remnants of Inhibitors,Modulators,Libraries ancient retroviral infections (Antony et al. 2004). The investigators showed that these repeats, which usually are heavily methylated, were less methylated in alcoholic brains, which was associated with their increased expression. Because ERVs constitute a significant part of the human genome, the study concluded that alcohol abuse causes global DNA hypomethylation in the brain, which is consistent with the majority of previous studies on alcohol-induced changes in DNA methylation. Manzardo and colleagues (2012) used immunological methods (i.e.

, immunoprecipitation) to isolate methylated DNA from alcoholics and control subjects and then applied this DNA to microarrays containing genomic promoter regions to identify promoters for which the methylation patterns differed between the two groups. The analyses Inhibitors,Modulators,Libraries found no differences between the groups in total methylation at the whole-genome level; however, about 20 percent of all promoters were differentially methylated between the groups, with less than half of these promoters showing greater methylation in alcoholics. These complementary findings suggest that chronic alcohol causes a general decrease in the overall number of methylated cytosines but also could lead to the de novo methylation of previously unmethylated nucleotides at the promoters of some genes. Such a combination Inhibitors,Modulators,Libraries of these Inhibitors,Modulators,Libraries processes already has been widely reported in studies of cancer, showing, for example, that methyl-deficient diets induce development of liver tumors (i.e., hepatocarcinogenesis) Inhibitors,Modulators,Libraries associated with global DNA hypomethylation and promoter hypermethylation at specific genes (Ehrlich 2005; Pogribny and Rusyn 2012). Hypomethylated states associated with cancer and other pathological conditions often are accompanied by a downregulation of the gene encoding DNMT1 Entinostat (Hervouet et al.