Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Shukron, O., Piras, V., Noordermeer, D., Holcman, D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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
_version_ 1783427721008775168
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
work_keys_str_mv AT shukrono statisticsofchromatinorganizationduringcelldifferentiationrevealedbyheterogeneouscrosslinkedpolymers
AT pirasv statisticsofchromatinorganizationduringcelldifferentiationrevealedbyheterogeneouscrosslinkedpolymers
AT noordermeerd statisticsofchromatinorganizationduringcelldifferentiationrevealedbyheterogeneouscrosslinkedpolymers
AT holcmand statisticsofchromatinorganizationduringcelldifferentiationrevealedbyheterogeneouscrosslinkedpolymers