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Toward understanding the dynamic state of 3D genome

The three-dimensional (3D) genome organization and its role in biological activities have been investigated for over a decade in the field of cell biology. Recent studies using live-imaging and polymer simulation have suggested that the higher-order chromatin structures are dynamic; the stochastic f...

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Autores principales: Shinkai, Soya, Onami, Shuichi, Nakato, Ryuichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Research Network of Computational and Structural Biotechnology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484532/
https://www.ncbi.nlm.nih.gov/pubmed/32952939
http://dx.doi.org/10.1016/j.csbj.2020.08.014
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author Shinkai, Soya
Onami, Shuichi
Nakato, Ryuichiro
author_facet Shinkai, Soya
Onami, Shuichi
Nakato, Ryuichiro
author_sort Shinkai, Soya
collection PubMed
description The three-dimensional (3D) genome organization and its role in biological activities have been investigated for over a decade in the field of cell biology. Recent studies using live-imaging and polymer simulation have suggested that the higher-order chromatin structures are dynamic; the stochastic fluctuations of nucleosomes and genomic loci cannot be captured by bulk-based chromosome conformation capture techniques (Hi-C). In this review, we focus on the physical nature of the 3D genome architecture. We first describe how to decode bulk Hi-C data with polymer modeling. We then introduce our recently developed PHi-C method, a computational tool for modeling the fluctuations of the 3D genome organization in the presence of stochastic thermal noise. We also present another new method that analyzes the dynamic rheology property (represented as microrheology spectra) as a measure of the flexibility and rigidity of genomic regions over time. By applying these methods to real Hi-C data, we highlighted a temporal hierarchy embedded in the 3D genome organization; chromatin interaction boundaries are more rigid than the boundary interior, while functional domains emerge as dynamic fluctuations within a particular time interval. Our methods may bridge the gap between live-cell imaging and Hi-C data and elucidate the nature of the dynamic 3D genome organization.
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spelling pubmed-74845322020-09-17 Toward understanding the dynamic state of 3D genome Shinkai, Soya Onami, Shuichi Nakato, Ryuichiro Comput Struct Biotechnol J Review Article The three-dimensional (3D) genome organization and its role in biological activities have been investigated for over a decade in the field of cell biology. Recent studies using live-imaging and polymer simulation have suggested that the higher-order chromatin structures are dynamic; the stochastic fluctuations of nucleosomes and genomic loci cannot be captured by bulk-based chromosome conformation capture techniques (Hi-C). In this review, we focus on the physical nature of the 3D genome architecture. We first describe how to decode bulk Hi-C data with polymer modeling. We then introduce our recently developed PHi-C method, a computational tool for modeling the fluctuations of the 3D genome organization in the presence of stochastic thermal noise. We also present another new method that analyzes the dynamic rheology property (represented as microrheology spectra) as a measure of the flexibility and rigidity of genomic regions over time. By applying these methods to real Hi-C data, we highlighted a temporal hierarchy embedded in the 3D genome organization; chromatin interaction boundaries are more rigid than the boundary interior, while functional domains emerge as dynamic fluctuations within a particular time interval. Our methods may bridge the gap between live-cell imaging and Hi-C data and elucidate the nature of the dynamic 3D genome organization. Research Network of Computational and Structural Biotechnology 2020-08-21 /pmc/articles/PMC7484532/ /pubmed/32952939 http://dx.doi.org/10.1016/j.csbj.2020.08.014 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review Article
Shinkai, Soya
Onami, Shuichi
Nakato, Ryuichiro
Toward understanding the dynamic state of 3D genome
title Toward understanding the dynamic state of 3D genome
title_full Toward understanding the dynamic state of 3D genome
title_fullStr Toward understanding the dynamic state of 3D genome
title_full_unstemmed Toward understanding the dynamic state of 3D genome
title_short Toward understanding the dynamic state of 3D genome
title_sort toward understanding the dynamic state of 3d genome
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484532/
https://www.ncbi.nlm.nih.gov/pubmed/32952939
http://dx.doi.org/10.1016/j.csbj.2020.08.014
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