Specific binding of the glucocorticoid-receptor complex to the mouse mammary tumor proviral promoter region

Abstract

To elucidate the molecular mechanism by which steroid hormones exert their regulatory function, we investigated the interaction of a glucocorticoid-receptor complex with purified DNA fragments from cloned mouse mammary tumor (MMTV) proviral DNA. With a DNA-cellulose binding assay, rat and mouse glucocorticoid receptors were found to interact with a high affinity site or sites in or near the promoter region of the MMTV proviral DNA. The assay allowed the use of unpurified as well as purified receptor, and therefore made it possible to investigate the binding properties of mutant receptors. Two nuclear-transfer-deficient receptors have a decreased affinity for specific as well as unspecific DNA, but are still capable of distinguishing between the two types of DNA. The existence of specific DNA binding sites for steroid-receptor complexes is discussed in the context of a general model of steroid hormone action.