Little things that count in transcriptional regulation

Although the NF-κB transcription factor tolerates significant sequence variations in its DNA binding site, NF-κB sites show remarkable evolutionary stability. In this issue of Cell, Leung et al. (2004) demonstrate that a single nucleotide change in an NF-κB binding site changes the dependence of the promoter on a specific coactivator without affecting NF-κB binding. These data suggest that binding sites may impart a specific configuration to bound transcription factors.