The research process, lead by Willaman Professor of Molecular Biology B. Franklin Pugh with Graduate Student Ho Sung Rhee, began by their using a molecular tool called an exonuclease to remove DNA that is not bound by one of the gene-regulating proteins. They then determined the nucleotide sequence for each of the remaining protein-bound DNA bundles -- the sequence of the four major component bases of DNA, labeled A, T, C, and G. "The advantage over other techniques of this technique, called ChIP-exo, is its ability to narrow down any binding location across millions and billions of nucleotide genomes to a certainty of about one nucleotide," Pugh said. "This improvement is roughly analogous to going from a low-resolution 240p television to a high-definition 1080p home-theater system. It provides an unprecedented view into how genes are regulated."
The ChIP-exo technique also removes a substantial amount of noise in the detection system that plagues other methods. The lower-noise technique reveals 2-to-5 times more binding locations, providing a much-more-complete picture of which genes are regulated by a particular protein, as well as a broader understanding of their structural organization across genomes. Having a more-complete picture allows scientists to understand in more detail how gene pathways work in normal human development, or fail to work in disease.