Chromatin architecture defines the glucocorticoid response

•Glucocorticoid receptor binding sites have a distinct chromatin architecture.•Preset chromatin accessibility defines specificity.•Glucocorticoid receptor relies on pioneer factors to preset binding sites.

The glucocorticoid receptor (GR) functions to regulate a wide group of physiological processes through hormone inducible interaction with genomic loci and subsequent manipulation of the transcriptional output of target genes. Despite expression in a wide variety of tissues, the GR has diverse roles that are regulated tightly in a cell type specific manner. With the advent of whole genome approaches, the details of that diversity and the mechanisms regulating them are beginning to be elucidated. This review aims describe the recent advances detailing the role chromatin structure plays in dictating GR specificity.