It is worth noting that these different methods can be combined, as, for example, ChIP-exo consists of an affinity-based step to isolate DNA associated with a protein of interest, followed by exonuclease digestion to precisely footprint the protein's binding site on DNA (Rhee and Pugh 2011). Similarly, several methods leverage analysis of modified DNA, or of DNA cleavage sites, in cells carrying fusion proteins in which the protein to be mapped is genetically fused to a modifying enzyme (such as DNA adenine methyltransferase (van Steensel and Henikoff 2000), thereby substituting a genetic fusion in place of the affinity-based step to provide specificity.
