Abstract: Methods, systems and kits for detecting protein-nucleic acid interactions, in particular, detecting the genomic location to near-base pair resolution at which a particular protein (e.g., transcription factor) binds includes combining steps of a conventional chromatin immunoprecipitation (ChIP) assay with use of an exonuclease that digests nucleic acid strands in the 5?-3? or 3?-5? direction until it reaches a bound protein including a protein crosslinked to the nucleic acid. Proteins that inefficiently crosslink to a nucleic acid and thus are very difficult to detect, are expected to be significantly detected by the kits and methods described herein.

Abstract: Methods, systems and kits for detecting protein-nucleic acid interactions, in particular, detecting the genomic location to near-base pair resolution at which a particular protein (e.g., transcription factor) binds includes combining steps of a convention chromatin immunoprecipitation (ChIP) assay with use of an exonuclease that digests DNA strands in the 5?-3? or 3?-5? direction until it reaches a bound protein including a protein crosslinked to DNA. A significant improvement of the resolution and dynamic range of the ChIP assay will increase one's ability to determine with confidence where a particular protein is binding in the genome. Importantly, proteins that inefficiently crosslink to DNA (either intrinsically or due to indirect crosslinking via another protein) and thus are very difficult to detect, are expected to be significantly detected by the kits and methods described herein.