Figure 4.

Summary of the interaction between hippocampal MR and NeuroD. Glucocorticoid response elements (GREs) previously inaccessible (1) could be rendered accessible by chromatin remodeling (one-way arrow) induced by NeuroD (2) binding at a nearby E-box (the NeuroD-specific sequence CAGATG). Upon ligand availability MR can bind an accessible GRE (3) in order to modulate transcriptional activity of its target genes. This interaction between NeuroD and MR (two-way arrow) is likely mediated via additional TF(s) in the transcriptional complex [9]. In forebrain MR knockout mice (4) GR is not compensating for the lack of MR binding at the MR-specific Rilpl1 site. Also at several MR/GR joint target sites (5) NeuroD occupancy is observed in the vicinity. Of note, we cannot discriminate between the binding of homo- and heterodimers in the present study. In absence of MR (6) GR binding is increased at the Per1 promoter, while for the other tested loci GR binding levels are unaltered. For sites that become GR-specific due to MR knockout, interactions with NeuroD remain to be explored, and other TF(s) might be involved (?). MR = mineralocorticoid receptor, GR = glucocorticoid receptor, GRE = glucocorticoid response element, TF = transcription factor, WT = wild type