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

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  • dc.contributor.author Nir, Guy
  • dc.contributor.author Farabella, Irene
  • dc.contributor.author Soler-Vila, Paula
  • dc.contributor.author Martí Renom, Marc A.
  • dc.contributor.author Wu, Chun-Ting
  • dc.date.accessioned 2019-12-04T08:33:07Z
  • dc.date.available 2019-12-04T08:33:07Z
  • dc.date.issued 2018
  • dc.description.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.
  • dc.description.sponsorship This work was supported by funds from Ministerio de Ciencia, Innovación y Universidades of Spain (http://www.ciencia.gob.es/) (IJCI-2015-23352) to IF, Damon Runyon Cancer Research Foundation (https://www.damonrunyon.org/) and Howard Hughes Medical Institute (https://www.hhmi.org/) to BJB, Uehara Memorial Foundation Research (https://www.taisho-holdings.co.jp/en/environment/social/sciences/) to HMS, William Randolph Hearst Foundation (https://www.hearstfdn.org/) to RBM, EMBO (Long-Term fellowship) (https://www.embo.org/) to JE, NSF (Center for Theoretical Biological Physics, Rice University) (https://www.nsf.gov/) to MDP and JNO, NSF (CCF-1054898, CCF-1317291) (https://www.nsf.gov/), NIH (1R01EB018659-01, 1-U01- MH106011-01) (https://www.nih.gov/), and Office of Naval Research (N00014-13-1-0593, N00014-14-1-0610, N00014-16-1-2182, N00014-16-1- 2410) (https://www.onr.navy.mil/) to PY, NIH (1DP2OD008540, U01HL130010, UM1HG009375, 4DP2OD008540) (https://www.nih.gov/), NSF (PHY-1427654) (https://www.nsf.gov/), USDA (2017-05741) (https://www.usda.gov/), Welch Foundation (Q-1866) (http://www.welch1.org/), NVIDIA (https://www.nvidia.com/en-us/), IBM (https://www.ibm.com/us-en/?lnk=m), Google (https://www.google.com/), Cancer Prevention Research Institute of Texas (R1304) (http://www.cprit.state.tx.us/), and McNair Medical Institute (http://www.mcnairfoundation.org/what-we-fund/mcnair-medical-institute/) to E.L.A., Horizon 2020 Research and Innovation Programme (676556) (https://ec.europa.eu/programmes/horizon2020/en/), European Research Council (609989) (https://erc.europa.eu/), Ministerio de Ciencia, Innovación y Universidades of Spain (BFU2017-85926-P) (http://www.ciencia.gob.es/), CERCA, and AGAUR Programme of the Generalitat de Catalunya and Centros de Excelencia Severo Ochoa (SEV-2012-0208) (http://www.ciencia.gob.es/portal/site/MICINN/menuitem.7eeac5cd345b4f34f09dfd1001432ea0/?vgnextoid=cba733a6368c2310VgnVCM1000001d04140aRCRD) to M.A.M-R., and NIH (5DP1GM106412, R01HD091797, R01GM123289) (https://www.nih.gov/) to C-tW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Nir 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.1007872
  • dc.identifier.doi http://dx.doi.org/10.1371/journal.pgen.1007872
  • dc.identifier.issn 1553-7390
  • dc.identifier.uri http://hdl.handle.net/10230/43080
  • dc.language.iso eng
  • dc.publisher Public Library of Science (PLoS)
  • dc.relation.ispartof PLOS Genetics. 2018;14(12):e1007872
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/676556
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-85926-P
  • dc.rights © 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.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Chromosome mapping
  • dc.subject.keyword Chromosome walking
  • dc.subject.keyword Chromosome structure and function
  • dc.subject.keyword Genomic libraries
  • dc.subject.keyword Homologous chromosomes
  • dc.subject.keyword Invertebrate genomics
  • dc.subject.keyword Imaging techniques
  • dc.subject.keyword Structural genomics
  • dc.title Walking along chromosomes with super-resolution imaging, contact maps, and integrative modeling
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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