In summary, our findings suggest that shortly after birth there is a wave of de novo methylation that results in the methylation of both CpG sites within the NGFIA consensus sequence. Such events would impede the binding of NGFIA to the exon 17 promoter. However, in the offspring of the high-LG mothers, NGFIA expression is increased to the point where binding occurs despite the “low affinity” status of the binding site. The binding of NGFIA is associated with histone acetylation and the subsequent availability of the site to demethylase. In support of this idea, the treatment of the adult offspring of the low-LG mothers with TSA increases H3 acetylation and NGFIA binding (see above) and results in the demethylation of the 5' CpG site of the NGFIA consensus sequence.67 While this model remains speculative (and controversial) at this time, these findings do suggest that modifications to the DNA methylation status in fully differentiated cells are clearly possible and pharmacologically reversible, an idea that holds considerable potential therapeutic implications.
