Complex genomic interactions in the dynamic regulation of transcription by the glucocorticoid receptor

• GR is recruited to response elements through complex interactions with the genome. • GR predominantly binds pre-programmed sites, but can be recruited to de novo sites. • GR binding at response elements is highly dynamic. • Ultradian fluctuations of glucocorticoids induce cyclic gene expression cycles.

The glucocorticoid receptor regulates transcriptional output through complex interactions with the genome. These events require continuous remodeling of chromatin, interactions of the glucocorticoid receptor with chaperones and other accessory factors, and recycling of the receptor by the proteasome. Therefore, the cohort of factors expressed in a particular cell type can determine the physiological outcome upon treatment with glucocorticoid hormones. In addition, circadian and ultradian cycling of hormones can also affect GR response. Here we will discuss revision of the classical static model of GR binding to response elements to incorporate recent findings from single cell and genome-wide analyses of GR regulation. We will highlight how these studies have changed our views on the dynamics of GR recruitment and its modulation of gene expression.