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 neurons results in the normalization of fetal alcohol exposure induced POMC gene silencing. However, MeCP2 knockdown did not alter POMC expression in hypothalamic neurons of controls although MeCP2 shRNA efficiently reduced its expression. The reason why MeCP2 knock down did not change POMC expression in AD, PF rat offsprings been it is known to recruit on to hypermethylated promoter to repress the transcription. The unmethylated or hypomethylated CpG islands were found to be devoid of MBDs as it has been reported for some tumor suppressor genes [46]. These results support the hypothesis that fetal alcohol exposure increases MeCP2 binding to CpG methylated POMC promoter and thereby prevents the transcription factor's ability to bind and activate gene transcription (Fig. 6). How MeCP2 recruits HDACs or HMTs onto the methylated POMC promoter to repress transcription in the fetal alcohol exposed condition is not known and it needs to be further investigated.
