Nir, GuyFarabella, IreneSoler-Vila, PaulaMartí Renom, Marc A.Wu, Chun-Ting2019-12-042019-12-042018Nir G, Farabella I, Pérez Estrada C, Ebeling CG, Beliveau BJ, Sasaki HM et al. Walking along chromosomes with super-resolution imaging, contact maps, and integrative modeling. PLoS Genet. 2018;14(12):e1007872. DOI: 10.1371/journal.pgen.10078721553-7390http://hdl.handle.net/10230/43080Chromosome organization is crucial for genome function. 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. Using the super-resolution microscopy methods of OligoSTORM and OligoDNA-PAINT, we trace 8 megabases of human chromosome 19, visualizing structures ranging in size from a few kilobases to over a megabase. Focusing on chromosomal regions that contribute to compartments, we discover distinct structures that, in spite of considerable variability, can predict whether such regions correspond to active (A-type) or inactive (B-type) compartments. Imaging through the depths of entire nuclei, we capture pairs of homologous regions in diploid cells, obtaining evidence that maternal and paternal homologous regions can be differentially organized. Finally, using restraint-based modeling to integrate imaging and Hi-C data, we implement a method-integrative modeling of genomic regions (IMGR)-to increase the genomic resolution of our traces to 10 kb.application/pdfeng© 2018 Nir et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1371/journal.pgen.1007872Chromosome mappingChromosome walkingChromosome structure and functionGenomic librariesHomologous chromosomesInvertebrate genomicsImaging techniquesStructural genomicsinfo:eu-repo/semantics/openAccess