title: Glucocorticoid receptor-dependent gene regulatory networks.
abstract: While the molecular mechanisms of glucocorticoid regulation of transcription have been studied in detail, the global networks regulated by the glucocorticoid receptor (GR) remain unknown. To address this question, we performed an orthogonal analysis to identify direct targets of the GR. First, we analyzed the expression profile of mouse livers in the presence or absence of exogenous glucocorticoid, resulting in over 1,300 differentially expressed genes. We then executed genome-wide location analysis on chromatin from the same livers, identifying more than 300 promoters that are bound by the GR. Intersecting the two lists yielded 53 genes whose expression is functionally dependent upon the ligand-bound GR. Further network and sequence analysis of the functional targets enabled us to suggest interactions between the GR and other transcription factors at specific target genes. Together, our results further our understanding of the GR and its targets, and provide the basis for more targeted glucocorticoid therapies.
authors.affiliation: Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Phuc Le
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Friedman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schug
authors.forename: John E
authors.initials: JE
authors.lastname: Brestelli
authors.forename: J Brandon
authors.initials: JB
authors.lastname: Parker
authors.forename: Irina M
authors.initials: IM
authors.lastname: Bochkis
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
mesh_terms: D000818:Animals; D002843:Chromatin; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D002843:Chromatin; D011965:Receptors, Glucocorticoid