Taken together these processes favor a repressive chromatin formation and inactivate early embryonic genes (Epsztejn-Litman et al., 2008). These studies suggest that instead of genomic context, such as presence of a CpG island, a better predictor of DNA methylation could be histone marks or the epigenomic status of the given loci. In the case of HDAC inhibitors, they are capable of inducing demethylation in the brain (Weaver et al., 2004). The HDAC inhibitor, Valproate has been used in neuropsychiatric disorders and recent findings show that it induces DNA demethylation in adult mouse brain (Dong, Chen, Gavin, Grayson, & Guidotti, 2010). Similarly, TSA and valproic acid have been shown to increase histone acetylation and decrease methylation. Interestingly in the same study 5-aza, only decreased methylation without affecting acetylation of H3 and H4 (Mitchell, Chen, Kundakovic, Costa, & Grayson, 2005). It is interesting to note that the class III histone deacetylase, SIRT1 has been shown to directly deacetylate DNMT1 at specific lysine residues and modulate its activity (Peng et al., 2011).
