title: Paired hormone response elements predict caveolin-1 as a glucocorticoid target gene.
abstract: Glucocorticoids act in part via glucocorticoid receptor binding to hormone response elements (HREs), but their direct target genes in vivo are still largely unknown. We developed the criterion that genomic occurrence of paired HREs at an inter-HRE distance less than 200 bp predicts hormone responsiveness, based on synergy of multiple HREs, and HRE information from known target genes. This criterion predicts a substantial number of novel responsive genes, when applied to genomic regions 10 kb upstream of genes. Multiple-tissue in situ hybridization showed that mRNA expression of 6 out of 10 selected genes was induced in a tissue-specific manner in mice treated with a single dose of corticosterone, with the spleen being the most responsive organ. Caveolin-1 was strongly responsive in several organs, and the HRE pair in its upstream region showed increased occupancy by glucocorticoid receptor in response to corticosterone. Our approach allowed for discovery of novel tissue specific glucocorticoid target genes, which may exemplify responses underlying the permissive actions of glucocorticoids.
authors.affiliation: Bioinformatics Laboratory, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marinus F
authors.initials: MF
authors.lastname: van Batenburg
authors.forename: Hualing
authors.initials: H
authors.lastname: Li
authors.forename: J Annelies
authors.initials: JA
authors.lastname: Polman
authors.forename: Servane
authors.initials: S
authors.lastname: Lachize
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Datson
authors.forename: Harmen J
authors.initials: HJ
authors.lastname: Bussemaker
authors.forename: Onno C
authors.initials: OC
authors.lastname: Meijer
mesh_terms: D000818:Animals; D001483:Base Sequence; D051242:Caveolin 1 / Q000235:genetics*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D051242:Caveolin 1; D017931:DNA Primers; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid