DNA methylation at CpG dinucleotides of gene promoters is a powerful means of gene silencing [35]. Fetal alcohol exposure induces aberrant changes in DNA methylation patterns with associated changes in expression of developmental and imprinting genes [36]. We recently reported fetal alcohol exposure increased POMC promoter methylation to reduce its transcript expression [21]. MeCP2, a member of the methyl CpG binding domain (MBD) containing family of proteins, binds methylated DNA and represses transcription by recruiting histone deacetylases (HDACs) [26], [37], [38] and histone methyl transferase (HMTs) [39], [40]. MeCP2 also targets several neuronal genes including BDNF and IGFBP3 [41]–[43]. Methylated CpG dinucleotides with adjacent A/T-rich sequences are putative MeCP2 binding sites [27]. The proximal POMC promoter contains a number of A/T-rich stretches in the vicinity of CpG sites. Loss of MeCP2 expression results in a loss of interaction of MeCP2 with methylated CpG sites at the promoter, thereby upregulating the expression of a subset of genes in Rett syndrome in mouse models as well as in human patients [44], [45]. In our study lentiviral knockdown of MeCP2 expression in hypothalamic
