Abstract
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.
Highlights
DNase-seq is a genomic technique that profiles chromatin accessibility
The DNase I enzyme is sterically hindered by compacted chromatin, tightly wound histones, and bound transcription factors and produces DNA cuts primarily in the accessible genome
We introduce BaseNormal, a base-pair resolution approach to normalization that corrects biases from DNase-capture data
Summary
DNase-seq is a genomic technique that profiles chromatin accessibility. In DNase-seq, intact nuclei are exposed to the DNase I enzyme. We introduce DNase-capture, a method that focuses DNase-seq analysis on selected genomic regions, resulting in a substantial increase in region-specific sequencing coverage. We introduce BaseNormal, a base-pair resolution approach to normalization that corrects biases from DNase-capture data.
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