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

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  • dc.contributor.author Di Stefano, Marco
  • dc.contributor.author Stadhouders, Ralph
  • dc.contributor.author Farabella, Irene
  • dc.contributor.author Castillo Andreo, David
  • dc.contributor.author Serra, François
  • dc.contributor.author Graf, T. (Thomas)
  • dc.contributor.author Marti-Renom, Marc A.
  • dc.date.accessioned 2020-10-22T06:28:28Z
  • dc.date.available 2020-10-22T06:28:28Z
  • dc.date.issued 2020
  • dc.description.abstract 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.
  • dc.description.sponsorship 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 CNAG
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Marco S, Stadhouders R, Farabella I, Castillo D, SerraF, Graf T et al. Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs. Nat Commun. 2020 May 22; 11(1): 2564. DOI: 10.1038/s41467-020-16396-1
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-020-16396-1
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/45554
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nature Communications. 2020 May 22;11(1):2564
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/676556
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-47736-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-85926-P
  • dc.rights © 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 made
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Cèl·lules
  • dc.subject.other Cromosomes
  • dc.title Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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