title: Coactivation of GR and NFKB alters the repertoire of their binding sites and target genes.
abstract: Glucocorticoid receptor (GR) exerts anti-inflammatory action in part by antagonizing proinflammatory transcription factors such as the nuclear factor kappa-b (NFKB). Here, we assess the crosstalk of activated GR and RELA (p65, major NFKB component) by global identification of their binding sites and target genes. We show that coactivation of GR and p65 alters the repertoire of regulated genes and results in their association with novel sites in a mutually dependent manner. These novel sites predominantly cluster with p65 target genes that are antagonized by activated GR and vice versa. Our data show that coactivation of GR and NFKB alters signaling pathways that are regulated by each factor separately and provide insight into the networks underlying the GR and NFKB crosstalk.
authors.affiliation: Department of Molecular Biology, Radboud University, Nijmegen, The Netherlands.
authors.forename: Nagesha A S
authors.initials: NA
authors.lastname: Rao
authors.forename: Melysia T
authors.initials: MT
authors.lastname: McCalman
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Moulos
authors.forename: Kees-Jan
authors.initials: KJ
authors.lastname: Francoijs
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Chatziioannou
authors.forename: Fragiskos N
authors.initials: FN
authors.lastname: Kolisis
authors.forename: Michael N
authors.initials: MN
authors.lastname: Alexis
authors.forename: Dimitra J
authors.initials: DJ
authors.lastname: Mitsiou
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D059372:Nucleotide Motifs; D020239:Receptor Cross-Talk / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000187:drug effects; D014222:Triamcinolone Acetonide / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D002843:Chromatin; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D014222:Triamcinolone Acetonide