Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming
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- dc.contributor.author Stadhouders, Ralphca
- dc.contributor.author Vidal Ocabo, Enriqueca
- dc.contributor.author Serra, Françoisca
- dc.contributor.author Di Stefano, Bruno, 1984-ca
- dc.contributor.author Le Dily, Françoisca
- dc.contributor.author Quilez Oliete, Javierca
- dc.contributor.author Gómez, Antonioca
- dc.contributor.author Collombet, Samuelca
- dc.contributor.author Berenguer, Claraca
- dc.contributor.author Cuartero, Yasminaca
- dc.contributor.author Hecht, Jochenca
- dc.contributor.author Filion, Guillaumeca
- dc.contributor.author Beato, Miguelca
- dc.contributor.author Martí Renom, Marc A.ca
- dc.contributor.author Graf, T. (Thomas)ca
- dc.date.accessioned 2018-06-14T07:43:14Z
- dc.date.issued 2018
- dc.description.abstract Chromosomal architecture is known to influence gene expression, yet its role in controlling cell fate remains poorly understood. Reprogramming of somatic cells into pluripotent stem cells (PSCs) by the transcription factors (TFs) OCT4, SOX2, KLF4 and MYC offers an opportunity to address this question but is severely limited by the low proportion of responding cells. We have recently developed a highly efficient reprogramming protocol that synchronously converts somatic into pluripotent stem cells. Here, we used this system to integrate time-resolved changes in genome topology with gene expression, TF binding and chromatin-state dynamics. The results showed that TFs drive topological genome reorganization at multiple architectural levels, often before changes in gene expression. Removal of locus-specific topological barriers can explain why pluripotency genes are activated sequentially, instead of simultaneously, during reprogramming. Together, our results implicate genome topology as an instructive force for implementing transcriptional programs and cell fate in mammals.
- dc.description.sponsorship This work was supported by the European Research Council under the 7th Framework Programme FP7/2007-2013 (ERC Synergy Grant 4D-Genome, grant agreement 609989 to T.G., G.J.F., M.A.M.-R. and M.B.) and the Ministerio de Educacion y Ciencia, SAF.2012-37167. R.S. was supported by an EMBO Long-term Fellowship (ALTF 1201-2014) and a Marie Curie Individual Fellowship (H2020-MSCA-IF-2014). We also acknowledge support from 'Centro de Excelencia Severo Ochoa 2013-2017' (SEV-2012-0208) and AGAUR to the CRG.
- dc.format.mimetype application/pdf
- dc.identifier.citation Stadhouders R, Vidal E, Serra F, Di Stefano B, Le Dily F, Quilez J et al. Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming. Nat Genet. 2018 Feb;50(2):238-49. DOI: 10.1038/s41588-017-0030-7.
- dc.identifier.doi http://dx.doi.org/10.1038/s41588-017-0030-7
- dc.identifier.issn 1061-4036
- dc.identifier.uri http://hdl.handle.net/10230/34895
- dc.language.iso eng
- dc.publisher Nature Publishing Groupca
- dc.relation.ispartof Nature Genetics. 2018 Feb;50(2):238-49
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-37167
- dc.rights © Nature Publishing Group. http://dx.doi.org/10.1038/s41588-017-0030-7
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.keyword Gene expression regulation
- dc.subject.keyword Cellular reprogramming
- dc.subject.keyword Induced pluripotent stem cells
- dc.subject.keyword Diploid cell
- dc.subject.keyword Klf4 gene
- dc.title Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogrammingca
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/acceptedVersion