DNase-capture reveals differential transcription factor binding modalities

We describe DNase-capture, an assay that increases the analytical resolution of DNase-seq by focusing its sequencing phase on selected genomic regions. We introduce a new method to compensate for capture bias called BaseNormal that allows for accurate recovery of transcription factor protection profiles from DNase-capture data. We show that these normalized data allow for nuanced detection of transcription factor binding heterogeneity with as few as dozens of sites.