STRUCTURAL DETERMINANTS OF A GLUCOCORTICOID RECEPTOR RECOGNITION ELEMENT

Analysis of the relative inducibility of an extensive series of mutant glucocorticoid response elements (GREs) defines features critical to the constitution of an active GRE. Assuming that function as a GRE reflects binding of gloucocorticoid receptor, our activity data are consist ent with the recognition of the GRE as two hexamer half-sites, each half- site recognized by a single subunit of a receptor dimer, probably in a cooperative fashion. Integrity of both half-sites is necessary for an active element, and spacing of the half-sites is critical. Identity of 1 basepair within the hexamer half-site is unconstrained; the receptor probably makes no base-specific contacts at this position. In contrast, at other position. In contrast, at other positions within the half-site, limited substitutions (if any) can be tolerated. These results along with data from certain insertion mutations suggest that the receptor recognizes each hexamer half-site as two separable subelements. A further inplication is that the DNA-binding domain of the glucocorticoid receptor is composed of distinct subdomains, which interact with the subelements of the recognition sequence.