Regulation of gene expression is primarily controlled by changes in the proteins that occupy genes’ regulatory elements. We developed genomic locus proteomics (GLoPro), in which we combine CRISPR-based genome targeting, proximity labeling, and quantitative proteomics to discover proteins associated with a specific genomic locus in native cellular contexts. After CRISPR-mediated targeting of the peroxidase APEX2 to a genomic locus of interest, the proteins at that locus are labeled, enriched and identified via quantitative proteomics.