DNA O-MAP uncovers the molecular neighborhoods associated with specific genomic loci

• DOI: 10.7554/elife.102489.1
• Publication Date: 2024-10-29T12:25:33Z
• Authors: Yuzhen Liu; Christopher D McGann; Mary Krebs; Thomas A Perkins; Rose Fields; Conor K Camplisson; David Z Nwizugbo; Chris Hsu; Shayan C Avanessian; Ashley F Tsue; Evan E Kania; David M Shechner; Brian J Beliveau; Devin K Schweppe

The accuracy of crucial nuclear processes such as transcription, replication, and repair, depends on the local composition of chromatin and the regulatory proteins that reside there. Understanding these DNA-protein interactions at the level of specific genomic loci has remained challenging due to technical limitations. Here, we introduce a method termed “DNA O-MAP”, which uses programmable peroxidase-conjugated oligonucleotide probes to biotinylate nearby proteins. We show that DNA O-MAP can be coupled with sample multiplexed quantitative proteomics and next-generation sequencing to quantify DNA-protein and DNA-DNA interactions at specific genomic loci.