Little things that count in transcriptional regulation.

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