Fig. 4.

DNA context and ligand dependent mineralocorticoid receptor (MR)/glucocorticoid receptors (GR) signaling. A. At high concentrations of agonist, MR and GR may bind as homo/or heterodimers to GREs, in conjunction with other, non-receptor, transcription factors (TFs). Depending on the DNA locus, coregulator complexes are recruited to mediate effects on transcription (arrows) and chromatin remodeling. Different ensembles of geometric shapes reflect different coregulator complexes. Other extracellular signals such as synaptic input can impinge at all levels via post-translational modifications (PTMs). B. When selective receptor modulators bind (here: for GR: a selective GR modulator or SGRM), the conformation of the receptor changes in such a way that only part of the interactions with coregulators may be formed. This allows for agonistic activity at some genes, but no or partial activity (antagonism) at others. Selective receptor modulation may allow to separate wanted from unwanted effects of MR/GR activation, although it is yet hard to predict which effects will separate.