Coactivation of GR and NFKB alters the repertoire of their binding sites and target genes

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

doi:10.1101/gr.118042.110

Coactivation of GR and NFKB alters the repertoire of their binding sites and target genes

¹Department of Molecular Biology, Radboud University, 6500 HB Nijmegen, The Netherlands;
²Metabolic Engineering and Bioinformatics Group, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, 11635 Athens, Greece;
³Molecular Endocrinology Programme, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, 11635 Athens, Greece

↵4 These authors contributed equally to this work.

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.

Footnotes

↵5 Corresponding authors.

E-mail h.stunnenberg{at}ncmls.ru.nl.

E-mail dmitsiou{at}eie.gr.
[Supplemental material is available for this article.]
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.118042.110.