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To regulate a particular gene, a transcription factor (TF) needs to bind aspecific genome location. How is this genome address specified amid thepresence of ~10^6-10^9 decoy sites? Our analysis of 319 known TF binding motifsclearly demonstrates that prokaryotes and eukaryotes use strikingly differentstrategies to target TFs to specific genome locations; eukaryotic TFs exhibitwidespread nonfunctional binding and require clustering of sites in regulatoryregions for specificity.

Fundamentally different strategies for transcriptional regulation are revealed by information-theoretical analysis of binding motifs