The glucocorticoid receptor is tethered to DNA-bound Oct-1 at the mouse gonadotropin-releasing hormone distal negative glucocorticoid response element

An element required for glucocorticoid repression of mouse gonadotropin-rel easing hormone (GnRH) gene transcription, the distal negative glucocorticoi d response element (nGRE), is not bound directly by glucocorticoid receptor s (GRs) but is recognized by Oct-1 present in GT1-7 cell nuclear extracts o r by Oct-1 purified from HeLa cells. Furthermore, purified full-length GRs interact directly with purified Oct-1 bound to the distal nGRE. Increasing the extent of distal nGRE: match to an Oct-1 consensus site not only increa ses the affinity of Oct-1 binding, but also alters the conformation of DNA- bound Oct-1 and the pattern of protein DNA complexes formed in vitro with G T1-7 cell nuclear extracts. In addition, the interaction of purified GR wit h DNA-bound Oct-1 is altered when Oct-1 is bound to the consensus Oct-1 sit e. Mutation of the distal nGRE to a consensus Oct-1 site is also associated with reduced glucocorticoid repression in transfected GT1-7 cells. Further more, repression of GnRN gene transcription by 12-O-tetradecanoylphorbol-13 -acetate, which utilizes sequences that overlap with the nGRE, is reversed by this distal nGRE mutation leading to activation of GnRH: gene transcript ion. Thus, changes in the assembly of multi-protein complexes at the distal nGRE can influence the regulation of GnRN gene transcription.