Walking along chromosomes with super-resolution imaging, contact maps, and integrative modeling
Cynthia Pérez Estrada,
Carl G. Ebeling,
Brian J. Beliveau,
Hiroshi M. Sasaki,
Soun H. Lee,
Son C. Nguyen,
Ruth B. McCole,
Jumana AlHaj Abed,
Nuno M. C. Martins,
Huy Q. Nguyen,
Mohammed A. Hannan,
Neva C. Durand,
Suhas S.P. Rao,
Jocelyn Y. Kishi,
Michele Di Pierro,
José N. Onuchic,
Erez L. Aiden,
Marc A. Marti-Renom,
Posted 28 Jul 2018
bioRxiv DOI: 10.1101/374058 (published DOI: 10.1371/journal.pgen.1007872)
Posted 28 Jul 2018
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 integrative modeling of genomic regions (IMGR) to increase the genomic resolution of our traces to 10 kb.
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