Walking along chromosomes with super-resolution imaging, contact maps, and integrative modeling
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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.
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Advances in super-resolution imaging enable visualisation of multiple interacting loci to the resolution of a few kilobases in single cells.
“advances in super-resolution imaging (reviewed in [500]) now enable the visualisation of multiple interacting loci to the resolution of a few kilobases in single cells [448, 501–503].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [502]
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- Authors
- Nir, G., Farabella, I., Pérez Estrada, C., Ebeling, C. G., Beliveau, B. J., Sasaki, H. M., Lee, S. D., Nguyen, S. C., McCole, R. B., Chattoraj, S., Erceg, J., AlHaj Abed, J., Martins, N. M. C., Nguyen, H. Q., Hannan, M. A., Russell, S., Durand, N. C., Rao, S. S. P., Kishi, J. Y., Soler-Vila, P., Di Pierro, M., Onuchic, J. N., Callahan, S. P., Schreiner, J. M., Stuckey, J. A., Yin, P., Aiden, E. L., Marti-Renom, M. A., & Wu, C.-T.
- Affiliations
- Harvard University (US)
- Barcelona Institute of Science and Technology (ES)
- Baylor College of Medicine (US)
- Broad Institute (US)
- Center for Theoretical Biological Physics (US)
- Corresponding author
- Stuckey, Jeff A.
- Yin, Peng
- Aiden, Erez Lieberman
- Wu, C.-ting
- ORCID
- Nir, Guy
- Farabella, Irene
- Ebeling, Carl G.
- Beliveau, Brian J.
- Sasaki, Hiroshi M.
- Lee, S. Dean
- Nguyen, Son C.
- McCole, Ruth B.
- Chattoraj, Shyamtanu
- AlHaj Abed, Jumana
- Martins, Nuno M. C.
- Nguyen, Huy Q.
- Hannan, Mohammed A.
- Russell, Sheikh
- Durand, Neva C.
- Rao, Suhas S. P.
- Kishi, Jocelyn Y.
- Soler-Vila, Paula
- Onuchic, José N.
- Callahan, Steven P.
- Schreiner, John M.
- Stuckey, Jeff A.
- Yin, Peng
- Aiden, Erez Lieberman
- Marti-Renom, Marc A.
- Wu, C.-ting
- Venue
- PLOS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-12-26
- Volume
- 14
- Issue
- 12
- Pages
- e1007872
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC6324821
- OpenAlex
- W2952052372
- Cited by
- 261
- References
- 9
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 20 · 2023: 22 · 2022: 34 · 2021: 61 · 2020: 54 · 2019: 31 · 2018: 1
- FWCI
- 14.23
- Type
- journal article
- Language
- en
- Update notices
- new_version (2019-01-08)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
- Rice Research Repository (Rice University) (submittedVersion, cc-by)
- Funders
- National Science Foundation (1054898, 1317291, 1427654)
- Howard Hughes Medical Institute
- U.S. Department of Agriculture (2017‐05741)
- Damon Runyon Cancer Research Foundation
- Cancer Prevention and Research Institute of Texas (R1304)
- Nvidia
- Rice University (1427654)
- Ministerio de Ciencia, Innovación y Universidades
- Centres de Recerca de Catalunya
- Generalitat de Catalunya
- Ministerio de Ciencia e Innovación (SEV-2012-0208, BFU2017‐85926‐P, IJCI-2015)
- National Institutes of Health (PHY-1427654, DP2OD008540)
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- National Heart, Lung, and Blood Institute (U01HL130010)
- Office of Naval Research (N00014-14-1-0610, N00014-16-1-2410, N00014-13-1- 0593, N00014-16-1-2182, N00014)
- National Institute of Mental Health (U01MH106011)
- National Human Genome Research Institute (UM1HG009375)
- National Institute of General Medical Sciences (DP1GM106412, R01GM123289)
- National Institute of Biomedical Imaging and Bioengineering (R01EB018659)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD091797)
- FP7 Ideas: European Research Council (609989)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- chromosome organization, 3D genome organization, Hi-C contact maps, integrative modeling, chromosome 19, homologous chromosome pairing
- MeSH terms
- Cells, Cultured, Chromosomes, Human, Pair 19, Female, Fluorescent Dyes, Humans, Male, Models, Genetic, Pedigree, Oligonucleotide Probes, Chromosome Walking, In Situ Hybridization, Fluorescence, Chromosome Painting, Imaging, Three-Dimensional, Chromosome Structures
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