Naomi Yamada, Matthew J Rossi, Nina Farrell, B Franklin Pugh, and Shaun Mahony
Nucleic Acids Research, gkaa618, https://doi.org/10.1093/nar/gkaa618
This article describes a new approach to characterizing the spatial organization of protein-DNA complexes using collections of ChIP-exo data. The approach takes advantage of a unique aspect of the high-resolution ChIP-exo assay; the shape of the sequenced read profiles generated by ChIP-exo at individual binding sites are reflective of the underlying protein-DNA crosslinking events. Performing ChIP-exo on different subunits within a given regulatory complex results in experimental profiles that contain subtle differences in shape and magnitude, dependent on the position of the subunit within the complex. The authors can characterize a given regulatory complex’s protein-DNA crosslinking profiles by simultaneously aligning ChIP-exo data from multiple protein subunits within the complex and across multiple binding regions. They can estimate the positions and relative strengths of individual protein-DNA crosslinking events within the aligned crosslinking profiles.