Fetal alcohol exposure is known to alter HPA axis activity partly via the suppression of POMC neuronal functions during adulthood [4], [28], [29]. We showed here that alcohol induced alteration of POMC neuronal functions involve hypermethylation of the POMC gene promoter and suppression of POMC gene transcription. We also provide evidence for a role of MeCP2 by showing an increased level of MeCP2 expression in POMC neurons in the hypothalamus of AF rats and by demonstrating a normalizing effect of MeCP2 shRNA on fetal alcohol-induced suppression of POMC gene expression and the HPA axis hyperresponse to LPS. These results suggest that MeCP2, a member of the MBD containing family of proteins, plays an important regulatory role in the epigenetic mechanism involved in fetal alcohol-induced alteration in POMC gene expression and its control of HPA axis function.
