The classic paper by Schmitz and Galas (1 ) established the usefulness of footprinting analysis for identifying protein-bound sites on DNA. The basis of the footprinting technique is that DNA-bound proteins protect the phosphodiester backbone of DNA from modification or cleavage by external agents, such as deoxyribonuclease. The technique is used most commonly to identify protected DNA sequences that are binding sites for transcription factors or other proteins involved in transcription initiation. When used in combination with other methods that confirm high-affinity protein-DNA interactions, such as electrophoretic mobility shift assay or chromatin immunoprecipitation, footprinting adds important evidence that delineates the residues critical for protein binding.