Paired hormone response elements predict caveolin-1 as a glucocorticoid target gene

• Published in: PloS one Vol. 5; no. 1; p. e8839
• Main Authors: van Batenburg, Marinus F, Li, Hualing, Polman, J Annelies, Lachize, Servane, Datson, Nicole A, Bussemaker, Harmen J, Meijer, Onno C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.01.2010; Public Library of Science (PLoS)
• Subjects: Animals; Base Sequence; Binding sites; Binomial distribution; Biochemistry; Bioinformatics; Caveolin; Caveolin 1 - genetics; Caveolin-1; Cell Line, Tumor; Chromatin Immunoprecipitation; Corticosterone; Criteria; Deoxyribonucleic acid; Diabetes and Endocrinology/Endocrinology; DNA; DNA Primers; Endocrinology; Gene expression; Genes; Genetics and Genomics/Bioinformatics; Genetics and Genomics/Gene Discovery; Genetics and Genomics/Gene Expression; Genomes; Glucocorticoids; Glucocorticoids - physiology; Hormones; Humans; In Situ Hybridization; Mice; Molecular biology; Molecular Biology/Bioinformatics; Molecular Biology/Transcription Initiation and Activation; Organs; Pharmacology; Proteins; Receptors, Glucocorticoid - physiology; Regulation; Regulatory sequences; RNA; Rodents; Spleen; Steroids (Organic compounds); Transcription, Genetic; New York; United States > US; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0008839

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.