Coactivation of GR and NFKB Alters the Repertoire of Their Binding Sites and Target Genes

Overview

Journal Genome Res

Specialty Genetics

Date 2011 Jul 14

PMID 21750107

Citations 125

Authors

Nagesha A S Rao

Melysia T McCalman

Panagiotis Moulos

Kees-Jan Francoijs

Aristotelis Chatziioannou

Fragiskos N Kolisis

Michael N Alexis

Dimitra J Mitsiou

Hendrik G Stunnenberg

Affiliations

Soon will be listed here.

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.

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