DNA footprinting is an in vitro method used to investigate protein binding to particular sections of DNA. This method smartly takes use of the fact that when a transcription factor binds to DNA with a specific affinity, the DNA is protected against destruction by nucleases.
Transcription factors bind to chromatin's cis-regulatory sequences. The protein is cross-linked to DNA and the chromatin is sheared to determine the genomic loci bound.
The main method for predicting transcription factor binding sites is to scan a DNA sequence of interest using a position weight matrix (PWM) for a transcription factor of interest, and several pattern-matching algorithms have been developed for this purpose.
A protein must have two characteristics in order to be classified as a transcription factor. 1) The ability to bind to DNA and 2) to recruit RNA polymerase/alter gene transcription.