Principles of dimer-specific gene regulation revealed by a comprehensive characterization of NF-κB family DNA binding

The unique DNA-binding properties of distinct NF-κB dimers are known to influence the selective regulation of NF-κB target genes. To gain a stronger appreciation for these dimer-specific differences, we have combined protein-binding microarrays (PBM) and surface plasmon resonance (SPR) to evaluate DNA sites recognized by eight different NF-κB dimers. We observed three distinct binding-specificity classes and provide insight into mechanisms by which dimers might regulate distinct sets of genes. We identified many new non-traditional κB site sequences and highlight an under-appreciated plasticity of NF-κB dimers in recognizing κB sites with a single consensus half-site. This study provides a database that will be of broad utility in efforts to identify NF-κB target sites and uncover gene regulatory circuitry.