Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs

Chromosome structure is a crucial regulatory factor for a wide range of nuclear processes. Chromosome conformation capture (3C)-based experiments combined with computational modelling are pivotal for unveiling 3D chromosome structure. Here, we introduce TADdyn, a tool that integrates time-course 3C...

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Autores: Di Stefano, Marco, Stadhouders, Ralph, Farabella, Irene, Castillo Andreo, David, Serra, François, Graf, T. (Thomas), Marti-Renom, Marc A.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/45554
Acceso en línea:http://hdl.handle.net/10230/45554
http://dx.doi.org/10.1038/s41467-020-16396-1
Access Level:acceso abierto
Palabra clave:Cèl·lules
Cromosomes
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spelling Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubsDi Stefano, MarcoStadhouders, RalphFarabella, IreneCastillo Andreo, DavidSerra, FrançoisGraf, T. (Thomas)Marti-Renom, Marc A.Cèl·lulesCromosomesChromosome structure is a crucial regulatory factor for a wide range of nuclear processes. Chromosome conformation capture (3C)-based experiments combined with computational modelling are pivotal for unveiling 3D chromosome structure. Here, we introduce TADdyn, a tool that integrates time-course 3C data, restraint-based modelling, and molecular dynamics to simulate the structural rearrangements of genomic loci in a completely data-driven way. We apply TADdyn on in situ Hi-C time-course experiments studying the reprogramming of murine B cells to pluripotent cells, and characterize the structural rearrangements that take place upon changes in the transcriptional state of 21 genomic loci of diverse expression dynamics. By measuring various structural and dynamical properties, we find that during gene activation, the transcription starting site contacts with open and active regions in 3D chromatin domains. We propose that these 3D hubs of open and active chromatin may constitute a general feature to trigger and maintain gene transcription.This work was partially supported by the European Research Council under the 7th Framework Program FP7/2007-2013 (ERC grant agreement 609989 to M.A.M-R. and T.G.), the European Union’s Horizon 2020 research and innovation programme (grant agreement 676556 to M.A.M-R.) and the Spanish Ministerio de Ciencia e Innovación (BFU2013-47736-P and BFU2017-85926-P to M.A.M-R. as well as IJCI-2015-23352 to I.F.). R.S. is supported by the Netherlands Organization for Scientific Research (VENI 91617114) and an Erasmus MC Fellowship. We also knowledge support from “Centro de Excelencia Severo Ochoa 2013-2017”, SEV-2012-0208 the Spanish ministry of Science and Innovation to the EMBL partnership and the CERCA Programme/Generalitat de Catalunya to the CRG. We also acknowledge support of the Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III, the Generalitat de Catalunya through Departament de Salut and Departament d’Empresa i Coneixement and the Co-financing by the Spanish Ministry of Science and Innovation with funds from the European Regional Development Fund (ERDF) corresponding to the 2014-2020 Smart Growth Operating Program to CNAGNature Research202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/45554http://dx.doi.org/10.1038/s41467-020-16396-1reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNature Communications. 2020 May 22;11(1):2564info:eu-repo/grantAgreement/EC/H2020/676556info:eu-repo/grantAgreement/EC/FP7/609989info:eu-repo/grantAgreement/ES/1PE/BFU2013-47736-Pinfo:eu-repo/grantAgreement/ES/2PE/BFU2017-85926-P© Marco Di Stefano et al. 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 madehttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/455542026-05-29T05:05:01Z
dc.title.none.fl_str_mv Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs
title Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs
spellingShingle Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs
Di Stefano, Marco
Cèl·lules
Cromosomes
title_short Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs
title_full Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs
title_fullStr Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs
title_full_unstemmed Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs
title_sort Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs
dc.creator.none.fl_str_mv Di Stefano, Marco
Stadhouders, Ralph
Farabella, Irene
Castillo Andreo, David
Serra, François
Graf, T. (Thomas)
Marti-Renom, Marc A.
author Di Stefano, Marco
author_facet Di Stefano, Marco
Stadhouders, Ralph
Farabella, Irene
Castillo Andreo, David
Serra, François
Graf, T. (Thomas)
Marti-Renom, Marc A.
author_role author
author2 Stadhouders, Ralph
Farabella, Irene
Castillo Andreo, David
Serra, François
Graf, T. (Thomas)
Marti-Renom, Marc A.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules
Cromosomes
topic Cèl·lules
Cromosomes
description Chromosome structure is a crucial regulatory factor for a wide range of nuclear processes. Chromosome conformation capture (3C)-based experiments combined with computational modelling are pivotal for unveiling 3D chromosome structure. Here, we introduce TADdyn, a tool that integrates time-course 3C data, restraint-based modelling, and molecular dynamics to simulate the structural rearrangements of genomic loci in a completely data-driven way. We apply TADdyn on in situ Hi-C time-course experiments studying the reprogramming of murine B cells to pluripotent cells, and characterize the structural rearrangements that take place upon changes in the transcriptional state of 21 genomic loci of diverse expression dynamics. By measuring various structural and dynamical properties, we find that during gene activation, the transcription starting site contacts with open and active regions in 3D chromatin domains. We propose that these 3D hubs of open and active chromatin may constitute a general feature to trigger and maintain gene transcription.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/45554
http://dx.doi.org/10.1038/s41467-020-16396-1
url http://hdl.handle.net/10230/45554
http://dx.doi.org/10.1038/s41467-020-16396-1
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nature Communications. 2020 May 22;11(1):2564
info:eu-repo/grantAgreement/EC/H2020/676556
info:eu-repo/grantAgreement/EC/FP7/609989
info:eu-repo/grantAgreement/ES/1PE/BFU2013-47736-P
info:eu-repo/grantAgreement/ES/2PE/BFU2017-85926-P
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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