Co-activation of GR and NFKB alters the repertoire of their binding sites and target genes
- Nagesha AS Rao1,
- Melysia T McCalman1,
- Panagiotis Moulos2,
- Kees-Jan Francoijs1,
- Aristotelis Chatziioannou2,
- Fragiskos N Kolisis2,
- Michael N Alexis2,
- Dimitra J Mitsiou2 and
- Hendrik G Stunnenberg1,3
- 1 Department of Molecular Biology, Radboud University;
- 2 Institute of Biological Research and Biotechnology, National Hellenic Research Foundation
- ↵* Corresponding author; email: h.stunnenberg{at}ncmls.ru.nl
Abstract
Glucocorticoid receptor (GR) exerts anti-inflammatory action in part by antagonizing pro-inflammatory transcription factors such as the nuclear factor kappa-b (NFKB). Here we assess the cross-talk of activated GR and RELA (p65, major NFKB component) by global identification of their binding sites and target genes. We show that cο-activation 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 co-activation 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.
- Received November 18, 2010.
- Accepted June 28, 2011.
- Copyright © 2011, Cold Spring Harbor Laboratory Press
