Glucocorticoids are central to homeostasis as a function of the circadian cycle, temporally preceding circulating adrenaline concentration circadian fluctuations. Virtually, all cell types express the glucocorticoid receptor (GR). GR is a transcription factor that activates gene expression by binding to enhancers. Intriguingly, not all cell types respond to GR stimulation in the same fashion at the molecular level. This indicates that GR activity is subject to epigenetic control. We discuss the molecular basis for epigenetic control of GR action at the genomic level, including the concept of topologically associating domains which may restrain the roaming range of distal enhancers. Furthermore, much evidence indicates that GR can repress gene expression programs. We therefore discuss current concepts of the molecular basis of GR-mediated gene expression repression, including non-genomic mechanisms that involve mRNA destabilization.
Part of the book: Corticosteroids