title: Glucocorticoid repression of the mouse gonadotropin-releasing hormone gene is mediated by promoter elements that are recognized by heteromeric complexes containing glucocorticoid receptor.
abstract: We have identified two regions of the mouse gonadotropin-releasing hormone (GnRH) promoter, one between -237 and -201 (distal element) and the other between -184 and -150 (proximal element), which are required for glucocorticoid repression in transiently transfected GT1-7 cells. These sequences show no similarity to known positive or negative glucocorticoid response elements (nGREs) and do not function when placed upstream of heterologous viral promoters. The glucocorticoid receptor (GR) does not bind directly to the distal or proximal promoter elements but may participate in glucocorticoid repression of GnRH gene transcription by virtue of its association within multiprotein complexes at these nGREs. Electrophoretic mobility shift assays with GT1-7 nuclear extract demonstrate the presence of GR-containing protein complexes on GnRH nGREs. One protein that co-occupies the distal nGRE in vitro along with GR is the POU domain transcription factor Oct-1. Thus, the tethering of GR to the GnRH distal nGRE, by virtue of a direct or indirect association with DNA-bound Oct-1, could play a role in hormone-dependent transcriptional repression of the GnRH gene. In contrast, Oct-1 does not appear to be a component of the GR-containing protein complex that is bound to the proximal nGRE.
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: U R
authors.initials: UR
authors.lastname: Chandran
authors.forename: B
authors.initials: B
authors.lastname: Attardi
authors.forename: R
authors.initials: R
authors.lastname: Friedman
authors.forename: Z w
authors.initials: Zw
authors.lastname: Zheng
authors.forename: J L
authors.initials: JL
authors.lastname: Roberts
authors.forename: D B
authors.initials: DB
authors.lastname: DeFranco
mesh_terms: D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D003852:Deoxyribonucleoproteins / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D018398:Homeodomain Proteins / Q000378:metabolism; D051863:Host Cell Factor C1; D051379:Mice; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004268:DNA-Binding Proteins; D003852:Deoxyribonucleoproteins; D005938:Glucocorticoids; C497693:Hcfc1 protein, mouse; D018398:Homeodomain Proteins; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; D009838:Oligodeoxyribonucleotides; C494166:Pou2f1 protein, mouse; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D007987:Gonadotropin-Releasing Hormone; D003907:Dexamethasone