Arginine vasopressin plays a pivotal role in the control of long-lasting effects of early-life stress on the brain. We previously reported that maternal separation in mice persistently upregulates Avp gene expression associated with reduced DNA methylation of a region in the Avp enhancer. This early-life stress-responsive region serves as a binding site for the methyl-CpG binding protein 2, which in turn is controlled through neuronal activity. We also found that the ability of methyl-CpG binding protein 2 to regulate transcription of the Avp gene and induce DNA methylation occurred through the recruitment of components of the epigenetic machinery. Understanding the sequential events involved in the epigenetic regulation of a gene should allow for targeted approaches aimed at reprogramming expression during development and possibly later life.