TY - JOUR
T1 - Coactivation of GR and NFKB alters the repertoire of their binding sites and target genes
AU - Rao, Nagesha A.S.
AU - McCalman, Melysia T.
AU - Moulos, Panagiotis
AU - Francoijs, Kees Jan
AU - Chatziioannou, Aristotelis
AU - Kolisis, Fragiskos N.
AU - Alexis, Michael N.
AU - Mitsiou, Dimitra J.
AU - Stunnenberg, Hendrik G.
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80052535611&partnerID=8YFLogxK
U2 - 10.1101/gr.118042.110
DO - 10.1101/gr.118042.110
M3 - Article
C2 - 21750107
AN - SCOPUS:80052535611
SN - 1088-9051
VL - 21
SP - 1404
EP - 1416
JO - Genome Research
JF - Genome Research
IS - 9
ER -