Department of Molecular Biology, Radboud University, Nijmegen, The Netherlands.
Genome Res. 2011 Sep;21(9):1404-16. doi: 10.1101/gr.118042.110. Epub 2011 Jul 12.
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.
糖皮质激素受体 (GR) 通过拮抗核因子 kappa-b (NFKB) 等促炎转录因子发挥抗炎作用。在这里，我们通过鉴定它们的结合位点和靶基因来评估激活的 GR 和 RELA（p65，主要的 NFKB 成分）之间的串扰。我们表明，GR 和 p65 的共激活改变了受调控基因的组成，并且以相互依赖的方式导致它们与新的位点结合。这些新的位点主要与被激活的 GR 拮抗的 p65 靶基因聚集，反之亦然。我们的数据表明，GR 和 NFKB 的共激活改变了由每个因子分别调节的信号通路，并深入了解了 GR 和 NFKB 串扰的网络。
