Walking along chromosomes with super-resolution imaging, contact maps, and integrative modeling

Abstract Chromosome structure is thought to be crucial for proper functioning of the nucleus. Here, we present a method for visualizing chromosomal DNA at super-resolution and then integrating Hi-C data to produce three-dimensional models of chromosome organization. We begin by applying Oligopaint probes and the single-molecule localization microscopy methods of OligoSTORM and OligoDNA-PAINT to image 8 megabases of human chromosome 19, discovering that chromosomal regions contributing to compartments can form distinct structures. Intriguingly, our data also suggest that homologous maternal and paternal regions may be differentially organized. Finally, we integrate imaging data with Hi-C and restraint-based modeling using a method called i ntegrative m odeling of g enomic r egions (IMGR) to increase the genomic resolution of our traces to 10 kb. One Sentence Summary Super-resolution genome tracing, contact maps, and integrative modeling enable 10 kb resolution glimpses of chromosome folding.