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

Chandran UR, Warren BS, Baumann CT, Hager GL, DeFranco DB. The glucocorticoid receptor is tethered to DNA-bound Oct-1 at the mouse GnRH distal negative glucocorticoid response element. J. Biol. Chem. 1999;274(0):2372-2378. PMID: 9891005

An element required for glucocorticoid repression of mouse gonadotropin-releasing hormone (GnRH) gene transcription, the distal negative glucocorticoid response element (nGRE), is not bound directly by glucocorticoid receptors (GRs) but is recognized by Oct-1 present in GT1-7 cell nuclear extracts or 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 increases 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 GT1-7 cell nuclear extracts. In addition, the interaction of purified GR with DNA-bound Oct-1 is altered when Oct-1 is bound to the consensus Oct-1 site. Mutation of the distal nGRE to a consensus Oct-1 site is also associated with reduced glucocorticoid repression in transfected GT1-7 cells. Furthermore, repression of GnRH 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 transcription. Thus, changes in the assembly of multi-protein complexes at the distal nGRE can influence the regulation of GnRH gene transcription.

Publication Year: 
1999
Faculty Author: 
Publication Credits: 
Chandran UR, Warren BS, Baumann CT, Hager GL, DeFranco DB.
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