Glucocorticoid receptor control of transcription: precision and plasticity via allostery

In response to steroid ligands, glucocorticoid receptor (GR) activates or represses gene expression in a highly context-specific manner. New evidence suggests that the conformation of GR is allosterically modulated by contextual signals, including DNA sequences, ligands, post-translational modifications and other transcription regulators, and that this supports the assembly of distinct transcription complexes. The glucocorticoid receptor (GR) is a constitutively expressed transcriptional regulatory factor (TRF) that controls many distinct gene networks, each uniquely determined by particular cellular and physiological contexts. The precision of GR-mediated responses seems to depend on combinatorial, context-specific assembly of GR-nucleated transcription regulatory complexes at genomic response elements. In turn, evidence suggests that context-driven plasticity is conferred by the integration of multiple signals, each serving as an allosteric effector of GR conformation, a key determinant of regulatory complex composition and activity. This structural and mechanistic perspective on GR regulatory specificity is likely to extend to other eukaryotic TRFs.