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Statistics of chromatin organization during cell differentiation revealed by heterogeneous cross-linked polymers
Chromatin of mammalian nucleus folds into discrete contact enriched regions such as Topologically Associating Domains (TADs). Folding hierarchy and internal organization of TADs is highly dynamic throughout cellular differentiation, and are correlated with gene activation and silencing. To account f...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572804/ https://www.ncbi.nlm.nih.gov/pubmed/31201308 http://dx.doi.org/10.1038/s41467-019-10402-x |
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author | Shukron, O. Piras, V. Noordermeer, D. Holcman, D. |
author_facet | Shukron, O. Piras, V. Noordermeer, D. Holcman, D. |
author_sort | Shukron, O. |
collection | PubMed |
description | Chromatin of mammalian nucleus folds into discrete contact enriched regions such as Topologically Associating Domains (TADs). Folding hierarchy and internal organization of TADs is highly dynamic throughout cellular differentiation, and are correlated with gene activation and silencing. To account for multiple interacting TADs, we developed a parsimonious randomly cross-linked (RCL) polymer model that maps high frequency Hi-C encounters within and between TADs into direct loci interactions using cross-links at a given base-pair resolution. We reconstruct three TADs of the mammalian X chromosome for three stages of differentiation. We compute the radius of gyration of TADs and the encounter probability between genomic segments. We found 1) a synchronous compaction and decompaction of TADs throughout differentiation and 2) high order organization into meta-TADs resulting from weak inter-TAD interactions. Finally, the present framework allows to infer transient properties of the chromatin from steady-state statistics embedded in the Hi-C/5C data. |
format | Online Article Text |
id | pubmed-6572804 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65728042019-06-24 Statistics of chromatin organization during cell differentiation revealed by heterogeneous cross-linked polymers Shukron, O. Piras, V. Noordermeer, D. Holcman, D. Nat Commun Article Chromatin of mammalian nucleus folds into discrete contact enriched regions such as Topologically Associating Domains (TADs). Folding hierarchy and internal organization of TADs is highly dynamic throughout cellular differentiation, and are correlated with gene activation and silencing. To account for multiple interacting TADs, we developed a parsimonious randomly cross-linked (RCL) polymer model that maps high frequency Hi-C encounters within and between TADs into direct loci interactions using cross-links at a given base-pair resolution. We reconstruct three TADs of the mammalian X chromosome for three stages of differentiation. We compute the radius of gyration of TADs and the encounter probability between genomic segments. We found 1) a synchronous compaction and decompaction of TADs throughout differentiation and 2) high order organization into meta-TADs resulting from weak inter-TAD interactions. Finally, the present framework allows to infer transient properties of the chromatin from steady-state statistics embedded in the Hi-C/5C data. Nature Publishing Group UK 2019-06-14 /pmc/articles/PMC6572804/ /pubmed/31201308 http://dx.doi.org/10.1038/s41467-019-10402-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Shukron, O. Piras, V. Noordermeer, D. Holcman, D. Statistics of chromatin organization during cell differentiation revealed by heterogeneous cross-linked polymers |
title | Statistics of chromatin organization during cell differentiation revealed by heterogeneous cross-linked polymers |
title_full | Statistics of chromatin organization during cell differentiation revealed by heterogeneous cross-linked polymers |
title_fullStr | Statistics of chromatin organization during cell differentiation revealed by heterogeneous cross-linked polymers |
title_full_unstemmed | Statistics of chromatin organization during cell differentiation revealed by heterogeneous cross-linked polymers |
title_short | Statistics of chromatin organization during cell differentiation revealed by heterogeneous cross-linked polymers |
title_sort | statistics of chromatin organization during cell differentiation revealed by heterogeneous cross-linked polymers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572804/ https://www.ncbi.nlm.nih.gov/pubmed/31201308 http://dx.doi.org/10.1038/s41467-019-10402-x |
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