Proximity Copy Paste: A methodology for single-molecule analysis of chromosome structure

Proximity Copy Paste: a methodology for single-molecule analysis of chromosome structure. Abstract Genomics assays that report protein occupancy or the 3D arrangement of crosslinked and fragmented chromosomes are often used to understand how genomic information is accessed, copied, or repaired. While powerful, such methods only interrogate a small fraction of the available information in a sample. Important questions related to whether events are coincident or mutually exclusive; or the nature of cause-effect relationships are difficult or impossible to assay. This proposal details the development of novel approaches to map the folding and protein occupancy of entire chromosomes, with single-nucleosome resolution and single-molecule precision. Our method employs a proximity labelling approach that can uniquely and indelibly tag DNA, protein or other molecules that associate in 3D space. Importantly, the method can easily be tuned to different resolutions, to allow quantitative measurements of proximity over a range of distances.