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Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models

The three-dimensional (3D) organization of chromosomes can be probed using methods like Capture-C. However, it is unclear how such population-level data relate to the organization within a single cell, and the mechanisms leading to the observed interactions are still largely obscure. We present a po...

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Autores principales: Brackley, Chris A., Brown, Jill M., Waithe, Dominic, Babbs, Christian, Davies, James, Hughes, Jim R., Buckle, Veronica J., Marenduzzo, Davide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815170/
https://www.ncbi.nlm.nih.gov/pubmed/27036497
http://dx.doi.org/10.1186/s13059-016-0909-0
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author Brackley, Chris A.
Brown, Jill M.
Waithe, Dominic
Babbs, Christian
Davies, James
Hughes, Jim R.
Buckle, Veronica J.
Marenduzzo, Davide
author_facet Brackley, Chris A.
Brown, Jill M.
Waithe, Dominic
Babbs, Christian
Davies, James
Hughes, Jim R.
Buckle, Veronica J.
Marenduzzo, Davide
author_sort Brackley, Chris A.
collection PubMed
description The three-dimensional (3D) organization of chromosomes can be probed using methods like Capture-C. However, it is unclear how such population-level data relate to the organization within a single cell, and the mechanisms leading to the observed interactions are still largely obscure. We present a polymer modeling scheme based on the assumption that chromosome architecture is maintained by protein bridges, which form chromatin loops. To test the model, we perform FISH experiments and compare with Capture-C data. Starting merely from the locations of protein binding sites, our model accurately predicts the experimentally observed chromatin interactions, revealing a population of 3D conformations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-0909-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-48151702016-04-01 Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models Brackley, Chris A. Brown, Jill M. Waithe, Dominic Babbs, Christian Davies, James Hughes, Jim R. Buckle, Veronica J. Marenduzzo, Davide Genome Biol Method The three-dimensional (3D) organization of chromosomes can be probed using methods like Capture-C. However, it is unclear how such population-level data relate to the organization within a single cell, and the mechanisms leading to the observed interactions are still largely obscure. We present a polymer modeling scheme based on the assumption that chromosome architecture is maintained by protein bridges, which form chromatin loops. To test the model, we perform FISH experiments and compare with Capture-C data. Starting merely from the locations of protein binding sites, our model accurately predicts the experimentally observed chromatin interactions, revealing a population of 3D conformations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-0909-0) contains supplementary material, which is available to authorized users. BioMed Central 2016-03-31 /pmc/articles/PMC4815170/ /pubmed/27036497 http://dx.doi.org/10.1186/s13059-016-0909-0 Text en © Brackley et al. 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Method
Brackley, Chris A.
Brown, Jill M.
Waithe, Dominic
Babbs, Christian
Davies, James
Hughes, Jim R.
Buckle, Veronica J.
Marenduzzo, Davide
Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models
title Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models
title_full Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models
title_fullStr Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models
title_full_unstemmed Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models
title_short Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models
title_sort predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815170/
https://www.ncbi.nlm.nih.gov/pubmed/27036497
http://dx.doi.org/10.1186/s13059-016-0909-0
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