repressor complex that includes methylated DNA binding proteins and HDACs. This hypothesis predicts that pharmacological activation of chromatin using HDAC inhibitors should result in activation of NGFIA binding and GR exon 17 promoter demethylation. However, the question is whether reversibility reflected in demethylation is limited to early life exclusively or whether it is possible to reverse these marks later in life as well if the appropriate signals to activate the chromatin structure are applied or by a pharmacological activation of chromatin structure. Our hypothesis is that the DNA methylation is a steady state of DNA methylation and demethylation whose direction is determined by the state of chromatin structure.99 ,110 This hypothesis predicts that both DNA methyltransferases and demethylases are present in adult neurons and that if the chromatin state is altered by either persistent physiological or pharmacological signals one should be able to change the state of methylation of a gene in postmitotic tissue, such as adult hippocampal neurons. We 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
