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Theoretical principles of transcription factor traffic on folded chromatin

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dc.contributor.author Cortini, Ruggero
dc.contributor.author Filion, Guillaume
dc.date.accessioned 2019-11-25T08:32:15Z
dc.date.available 2019-11-25T08:32:15Z
dc.date.issued 2018
dc.identifier.citation Cortini R, Filion GJ. Theoretical principles of transcription factor traffic on folded chromatin. Nat Commun. 2018;9(1):1740. DOI: 10.1038/s41467-018-04130-x
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/42953
dc.description.abstract All organisms regulate transcription of their genes. To understand this process, a complete understanding of how transcription factors find their targets in cellular nuclei is essential. The DNA sequence and other variables are known to influence this binding, but the distribution of transcription factor binding patterns remains mostly unexplained in metazoan genomes. Here, we investigate the role of chromosome conformation in the trajectories of transcription factors. Using molecular dynamics simulations, we uncover the principles of their diffusion on chromatin. Chromosome contacts play a conflicting role: at low density they enhance transcription factor traffic, but at high density they lower it by volume exclusion. Consistently, we observe that in human cells, highly occupied targets, where protein binding is promiscuous, are found at sites engaged in chromosome loops within uncompacted chromatin. In summary, we provide a framework for understanding the search trajectories of transcription factors, highlighting the key contribution of genome conformation.
dc.description.sponsorship We acknowledge the financial support of the Spanish Ministry of Economy and Competitiveness (Centro de Excelencia Severo Ochoa 2013–2017, SEV-2012–0208, Plan Nacional BFU2012-37168), of the CERCA Programme/Generalitat de Catalunya, of the European Research Council (ERC Synergy Grant 609989), and of the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement 608959.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nature Communications. 2018;9(1):1740
dc.rights © The Author(s) 2018. 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/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Theoretical principles of transcription factor traffic on folded chromatin
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41467-018-04130-x
dc.subject.keyword Biological physics
dc.subject.keyword Biopolymers in vivo
dc.subject.keyword Chromatin structure
dc.subject.keyword Computational models
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-37168
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/608959
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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