Journal Article

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

Stuckey, Jeff A., Sasaki, Hiroshi M., Russell, Sheikh, Schreiner, John M., Durand, Neva C., Callahan, Steven P., Martins, Nuno M. C., Ebeling, Carl G., Soler-Vila, Paula, Yin, Peng, Lee, S. Dean, Aiden, Erez Lieberman, Wu, C.-ting, Rao, Suhas S. P., Marti-Renom, Marc A., McCole, Ruth B., Di Pierro, Michele, Onuchic, José N., Nir, Guy, Erceg, Jelena, Nguyen, Son C., Chattoraj, Shyamtanu, Kishi, Jocelyn Y., Farabella, Irene, AlHaj Abed, Jumana, Hannan, Mohammed A., Beliveau, Brian J., Pérez Estrada, Cynthia, Nguyen, Huy Q.

2018

Overview

Chromosome 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Architectural engineering / Biology / Biology and Life Sciences / Cells, Cultured / Chromosome 19 / Chromosome Painting - methods / Chromosome Structures - chemistry / Chromosome Structures - genetics / Chromosome Structures - ultrastructure / Chromosome Walking - methods / Chromosomes / Chromosomes, Human, Pair 19 - chemistry / Chromosomes, Human, Pair 19 - genetics / Chromosomes, Human, Pair 19 - ultrastructure / Engineering / Female / Fluorescent Dyes / Funding / Gene mapping / Genomes / Humans / Imaging, Three-Dimensional / In Situ Hybridization, Fluorescence - methods / Localization / Male / Medical research / Medical schools / Medicine / Methods / Microscopy / Models, Genetic / Oligonucleotide Probes / Pedigree / Physics / Research and Analysis Methods / Software / Supervision / Visualization