Alternate approaches use HDAC inhibition to regulate DNA methylation. It is well established that DNA methylation and histone modifications are interdependent and lead to coordinated patterns of regulation that modulate various phenotypes such as learning and memory, synaptic plasticity, somatic cell reprogramming and cancer biology (Cedar & Bergman, 2009; Miller, Campbell, & Sweatt, 2008). Marking sites with active methylated H3K4 appears to be one of the ways for CpG island-rich promoters in somatic cells to prevent DNA methylation and thus protected from de novo methylation (Weber et al., 2007). These findings are consistent with other studies where increased DNA methylation has been shown to be associated with the absence of H3K4 methylation and the presence of H3K9 methylation (Meissner et al., 2008). In alcoholic post-mortem brain, loci of hypomethylation have been well correlated with increased histone H3K4 trimethylation (Ponomarev, Wang, Zhang, Harris, & Mayfield, 2012). The histone methyltransferase G9a has been shown to exhibit dual functionality through SET domain- mediated H3K9 tri-methylation mediated heterochromatin formation as well as ANK domain- recruitment of DNMT3a and 3b to initiate de novo methylation.
