previously established that pharmacological activation of chromatin structure by HDAC inhibitors can trigger replication-independent active demethylation of DNA.108,130,131 We tested our hypothesis that the demethylation of the GR exon 17 promoter is driven by histone acetylation and could be activated in adult neurons as well; HDAC inhibition should reverse the effects of cytosine methylation on NGFIA binding to the exon 17 promoter, GR expression, and HPA responses to stress. We used a central infusion of adult offspring of high- or low-LG mothers with the HDAC inhibitor, trichostatin A (TSA), for 4 consecutive days. As expected, ChIP assays revealed that HDAC inhibition through TSA infusion significantly increased the level of acetylated H3 at the exon 17 site (ie, HDAC inhibition resulted in increased histone acetylation) in the offspring of lowLG mothers to levels comparable to those observed in the offspring of high-LG mothers. The increased histone acetylation is associated with enhanced NGFIA binding to the exon 17 promoter sequence and completely eliminates the effect of maternal care. As expected, enhanced NGFIA binding to the exon 17 promoter increased hippocampal GR expression. Hippocampal GR expression in the TSA-treated adult offspring of low-LG mothers was indistinguishable from that of the high-LG groups. Most
