Molecular Determinants of Positive and Negative Regulation by Ligand-Regulated Transcription Factors

Abstract

The cloning of the glucocorticoid and estrogen receptors (1–5) permitted identification of a super-family of ligand-regulated transcription factors (e.g., 6–12), including the c-erb A gene products, which bound thyroid hormone (9,11). Knowledge of the structure of these transcription factors has permitted initial exploration of the functional domains. In the case of the glucocorticoid receptor, the DNA binding domain has been identified and appears to be sufficient for stimulation of transcription (13–17). In this manuscript, we review data regarding the regulation of rat prolactin and growth hormone gene expression by the estrogen and thyroid hormone receptors, respectively. The cis-active elements and the molecular determinants of positive and negative regulation of the prolactin gene by estrogen are defined. The T3 regulatory element in the rat growth hormone gene is defined, using an avidin/biotin complex DNA (ABCD) binding assay, and demonstrated to bind the c-erb A gene product.