DNase l hypersensitive sites sequencing (DNase-Seq) is based on a well-established DNase I footprinting protocol that was optimized for sequencing . In this method, DNA-protein complexes are treated with DNase l, and the DNA is then extracted and sequenced. Sequences bound by regulatory proteins are protected from DNase l digestion. Deep sequencing provides accurate representation of the location of regulatory proteins in genome. In a variation on this approach, the DNA-protein complexes are stabilized by formaldehyde crosslinking before DNase I digestion. The crosslinking is reversed before DNA purification. In an alternative modification, called GeF-Seq, both the crosslinking and the DNase I digestion are carried out in vivo, within permeabilized cells .