A steroid hormone crosses the lipid bilayer and binds an intracellular nuclear receptor. For a cytoplasmic glucocorticoid receptor, ligand binding alters association with molecular chaperones, exposes nuclear-targeting functions and promotes accumulation in the cell nucleus. Other steroid hormone receptors already have substantial nuclear localization. The activated receptor binds specific hormone response elements in DNA, often as a dimer, and changes recruitment of transcription coactivators or transcription corepressors. These factors alter local chromatin and recruitment or activity of the RNA polymerase II machinery. The result is selective activation or repression of target genes, followed by altered messenger RNA and protein abundance; the hormone itself does not act as an RNA polymerase or directly rewrite the DNA sequence.