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

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

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere1007872
JournalPLoS genetics
Volume14
Issue number12
DOIs
StatePublished - Dec 2018
Externally publishedYes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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