The simplest application of this technique is to assess whether a given protein binds to a region of interest within a DNA molecule. Polymerase chain reaction (PCR) amplify and label region of interest that contains a potential protein-binding site, ideally amplicon is between 50 and 200 base pairs in length. Add protein of interest to a portion of the labeled template DNA; a portion should remain separate without protein, for later comparison. Add a cleavage agent to both portions of DNA template.  The cleavage agent is a chemical or enzyme that will cut at random locations in a sequence independent manner.  The reaction should occur just long enough to cut each DNA molecule in only one location.  A protein that specifically binds a region within the DNA template will protect the DNA it is bound to from the cleavage agent. Run both samples side by side on a polyacrylamide gel electrophoresis.  The portion of DNA template without protein will be cut at random locations, and thus when it is run on a gel, will produce a ladder-like distribution.  The DNA template with the protein will result in ladder distribution with a break in it, the "footprint", where the DNA has been protected from the cleavage agent.
Note: Maxam-Gilbert chemical DNA sequencing can be run alongside the samples on the polyacrylamide gel to allow the prediction of the exact location of ligand binding site.