Fig. 6

The GR DBD binds to a cryptic sequence in the spacer of NF-κB response elements. a Crystal structure of the p50/p65 NF-κB heterodimer bound to its cognate response element in the IFNβ promoter⁷¹. The GR-binding footprint (AATTY sequence) at this response element is shown in red. At this element (and many of its other response elements), NF-κB largely makes sequence-specific contacts with the regions flanking the AATTY motif (see insets). However, despite the lack of sequence-specific contacts by NF-κB in this spacer region, the AATTY motif is highly conserved; the conservation of the AATTY motif within the IL8 NF-κB response element is shown in b. c In addition, the GR DBD can bind to the IL8 NF-κB response element from divergent species with nearly-identical affinities. d Finally, mutation of central, conserved bases within the AATTY motif of the IL8 promoter affects the ability of dexamethasone to repress transcription from this response element in HeLa cells. *p < 0.001 of TNF-α vs. no treatment; ^p < 0.001 of TNF-α vs. TNF-α + Dex; NS, no significance between TNF-α vs. TNF-α + Dex. Statistics are two-way ANOVA with Tukey’s post-hoc test.