DNA methylation of a limited number of sites in the exon 1F NR3C1 promoter was associated with decreased expression of the glucocorticoid receptor 1F variant and of total glucocorticoid receptor mRNA in suicide victims with a history of childhood abuse. Defining a causal relation between the methylation status and transcriptional efficiency of the NR3C1 promoter is therefore of great importance. We hypothesized that DNA methylation regulates the expression of the NR3C1 promoter through alterations in transcription factor binding. The transcription factor NGFI-A regulates the expression of Nr3c1 promoter in the rat, an effect that is inhibited by DNA methylation17. To our knowledge, the regulation of NGFI-A (also known as Zif268, EGR1, Krox-24 and ZENK) has not been studied in the human hippocampus, although there is evidence that its expression is downregulated in the prefrontal cortex in schizophrenia26. The NR3C1 promoter contains a number of canonical and noncanonical NGFI-A recognition elements (Fig. 3a). We wondered whether, as in the rat17, NGFI-A could regulate gene transcription through the NR3C1 promoter and whether this effect might be influenced by the methylation status of
