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Spatial confinement is a major determinant of the folding landscape of human chromosomes

The global architecture of the cell nucleus and the spatial organization of chromatin play important roles in gene expression and nuclear function. Single-cell imaging and chromosome conformation capture-based techniques provide a wealth of information on the spatial organization of chromosomes. How...

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Autores principales: Gürsoy, Gamze, Xu, Yun, Kenter, Amy L., Liang, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117743/
https://www.ncbi.nlm.nih.gov/pubmed/24990374
http://dx.doi.org/10.1093/nar/gku462
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author Gürsoy, Gamze
Xu, Yun
Kenter, Amy L.
Liang, Jie
author_facet Gürsoy, Gamze
Xu, Yun
Kenter, Amy L.
Liang, Jie
author_sort Gürsoy, Gamze
collection PubMed
description The global architecture of the cell nucleus and the spatial organization of chromatin play important roles in gene expression and nuclear function. Single-cell imaging and chromosome conformation capture-based techniques provide a wealth of information on the spatial organization of chromosomes. However, a mechanistic model that can account for all observed scaling behaviors governing long-range chromatin interactions is missing. Here we describe a model called constrained self-avoiding chromatin (C-SAC) for studying spatial structures of chromosomes, as the available space is a key determinant of chromosome folding. We studied large ensembles of model chromatin chains with appropriate fiber diameter, persistence length and excluded volume under spatial confinement. We show that the equilibrium ensemble of randomly folded chromosomes in the confined nuclear volume gives rise to the experimentally observed higher-order architecture of human chromosomes, including average scaling properties of mean-square spatial distance, end-to-end distance, contact probability and their chromosome-to-chromosome variabilities. Our results indicate that the overall structure of a human chromosome is dictated by the spatial confinement of the nuclear space, which may undergo significant tissue- and developmental stage-specific size changes.
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spelling pubmed-41177432014-08-15 Spatial confinement is a major determinant of the folding landscape of human chromosomes Gürsoy, Gamze Xu, Yun Kenter, Amy L. Liang, Jie Nucleic Acids Res Computational Biology The global architecture of the cell nucleus and the spatial organization of chromatin play important roles in gene expression and nuclear function. Single-cell imaging and chromosome conformation capture-based techniques provide a wealth of information on the spatial organization of chromosomes. However, a mechanistic model that can account for all observed scaling behaviors governing long-range chromatin interactions is missing. Here we describe a model called constrained self-avoiding chromatin (C-SAC) for studying spatial structures of chromosomes, as the available space is a key determinant of chromosome folding. We studied large ensembles of model chromatin chains with appropriate fiber diameter, persistence length and excluded volume under spatial confinement. We show that the equilibrium ensemble of randomly folded chromosomes in the confined nuclear volume gives rise to the experimentally observed higher-order architecture of human chromosomes, including average scaling properties of mean-square spatial distance, end-to-end distance, contact probability and their chromosome-to-chromosome variabilities. Our results indicate that the overall structure of a human chromosome is dictated by the spatial confinement of the nuclear space, which may undergo significant tissue- and developmental stage-specific size changes. Oxford University Press 2014-09-01 2014-07-02 /pmc/articles/PMC4117743/ /pubmed/24990374 http://dx.doi.org/10.1093/nar/gku462 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Computational Biology
Gürsoy, Gamze
Xu, Yun
Kenter, Amy L.
Liang, Jie
Spatial confinement is a major determinant of the folding landscape of human chromosomes
title Spatial confinement is a major determinant of the folding landscape of human chromosomes
title_full Spatial confinement is a major determinant of the folding landscape of human chromosomes
title_fullStr Spatial confinement is a major determinant of the folding landscape of human chromosomes
title_full_unstemmed Spatial confinement is a major determinant of the folding landscape of human chromosomes
title_short Spatial confinement is a major determinant of the folding landscape of human chromosomes
title_sort spatial confinement is a major determinant of the folding landscape of human chromosomes
topic Computational Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117743/
https://www.ncbi.nlm.nih.gov/pubmed/24990374
http://dx.doi.org/10.1093/nar/gku462
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