epigenomic status of the exon 17 GR promoter. The developmental timecourse study is critical. Recall that the 5' CpG dinucleotide of the NGFIA consensus sequence of the exon 17 promoter is methylated to the same, elevated level in the newborn offspring of high- and low-LG mothers. It is only over the first week of life that the difference emerges, with the decline in the methylation of the 5' CpG site in the offspring of high-LG, but not low-LG mothers. No such demethylation occurs at the neighboring 3' CpG site. The impressive selectivity suggests a demethyaltion process that is targeted in some manner. It is critical to define the processes by which such apparently active demethylation might occur. Regardless of these as-yet unanswered questions, these findings provide the first evidence that maternal behavior stably alters the epigenome of the offspring, providing a mechanism for the long-term effects of early experience on gene expression in the adult. These studies offer an opportunity to clearly define the nature of gene-environment interactions during development and how such effects result in the sustained “environmental programming” of gene expression and function over the life span. Finally, it is important to note that maternal effects on the
