title: Structural determinants of a glucocorticoid receptor recognition element.
abstract: 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 glucocorticoid receptor, our activity data are consistent 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. The 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 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 implication is that the DNA-binding domain of the glucocorticoid receptor is composed of distinct subdomains, which interact with the subelements of the recognition sequence.
authors.affiliation: Department of Pathology, University of Colorado Health Sciences Center, Denver 80262.
authors.forename: S K
authors.initials: SK
authors.lastname: Nordeen
authors.forename: B J
authors.initials: BJ
authors.lastname: Suh
authors.forename: B
authors.initials: B
authors.lastname: Kühnel
authors.forename: C A
authors.initials: CA
authors.lastname: Hutchison
mesh_terms: D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004247:DNA / Q000378:metabolism*; D046911:Macromolecular Substances; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000235:genetics; D011487:Protein Conformation; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000235:genetics*
chemical_list: D046911:Macromolecular Substances; D011965:Receptors, Glucocorticoid; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase