The glucocorticoid receptor synergizes with Jun homodimers to activate AP-1-regulated promoters lacking GR binding sites.

Jun/Fos (AP-1) and steroid hormone receptors (SHR) are distinct families of transcription factors that convert extracellular signals into long-term genetic responses. Despite clear differences in their modes of activation and DNA binding specificities, a regulatory cross-talk between AP-1 and SHR such as the glucocorticoid receptor (GR), has been established. Here, we show that the hormone-activated GR negatively or positively modulates the expression of AP-1-dependent genes, depending on the subunits of the dimeric AP-1 complex. This type of regulation does not depend on the presence of a GR binding site in the promoter and is mediated through the DNA binding domain of Jun. Since individual subunits of AP-1 exhibit small differences in sequence specificity, specific subsets of AP-1-dependent genes may be regulated by steroid hormones in different directions.