The relationship between nanoscale genome organization and gene expression in mouse embryonic stem cells during pluripotency transition

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  • dc.contributor.author Garate,, Ximena
  • dc.contributor.author Gómez García, Pablo Aurelio
  • dc.contributor.author Fernández Merino, Manuel
  • dc.contributor.author Cadevall Anglès, Marta
  • dc.contributor.author Zhu, Chenggan
  • dc.contributor.author Castells García, Àlvaro, 1991-
  • dc.contributor.author Ed-Daoui, Ilyas
  • dc.contributor.author Martin, Laura
  • dc.contributor.author Ochiai, Hiroshi
  • dc.contributor.author Neguembor, Maria Victoria
  • dc.contributor.author Cosma, Maria Pia
  • dc.date.accessioned 2024-12-02T07:17:17Z
  • dc.date.available 2024-12-02T07:17:17Z
  • dc.date.issued 2024
  • dc.description.abstract During early development, gene expression is tightly regulated. However, how genome organization controls gene expression during the transition from naïve embryonic stem cells to epiblast stem cells is still poorly understood. Using single-molecule microscopy approaches to reach nanoscale resolution, we show that genome remodeling affects gene transcription during pluripotency transition. Specifically, after exit from the naïve pluripotency state, chromatin becomes less compacted, and the OCT4 transcription factor has lower mobility and is more bound to its cognate sites. In epiblast cells, the active transcription hallmark, H3K9ac, decreases within the Oct4 locus, correlating with reduced accessibility of OCT4 and, in turn, with reduced expression of Oct4 nascent RNAs. Despite the high variability in the distances between active pluripotency genes, distances between Nodal and Oct4 decrease during epiblast specification. In particular, highly expressed Oct4 alleles are closer to nuclear speckles during all stages of the pluripotency transition, while only a distinct group of highly expressed Nodal alleles are in close proximity to Oct4 when associated with a nuclear speckle in epiblast cells. Overall, our results provide new insights into the role of the spatiotemporal genome remodeling during mouse pluripotency transition and its correlation with the expression of key pluripotency genes.
  • dc.description.sponsorship European Union's Horizon 2020 research and innovation programme [686637 (CellViewer) and 964342 (Ecabox) to M.P.C.]; Ministerio de Ciencia e Innovación [PID2020-114080GB-I00/ AEI / 10.13039/501100011033, BFU2017-86760-P (AEI/FEDER, UE) to M.P.C.]; AGAUR grant from Secretaria d’Universitats i Recerca del Departament d’Empresa iConeixement de la Generalitat de Catalunya [2017 SGR 689 and 2021-SGR2021-01300]; Fundació La Marató de TV3 [202027-10 to M.P.C.]; National Natural Science Foundation of China [31971177 and 32270577 to M.P.C., and 3221101299 to A.C.G.]; The Innovative Team Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110103001 to M.P.C.]; The Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology [20200730009 to M.P.C.]; INTREPiD Postdoctoral Programme cofunded by the European Commission [754422 to X.G.]; People Program (Marie Curie Actions) FP7/2007–2013 under REA [608959 to M.V.N.]; Juan de la Cierva-Incorporación 2017 [to M.V.N.]; Grant for the recruitment of early-stage research staff FI-2020 [Operational Program of Catalonia 2014-2020 CCI grant no. 2014ES05SFOP007 of the European Social Fund to L.M.]; La Caixa’ Foundation fellowship [LCF/BQ/DR20/11790016 to L.M.].
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Garate X, Gómez-García PA, Merino MF, Angles MC, Zhu C, Castells-García A, et al. The relationship between nanoscale genome organization and gene expression in mouse embryonic stem cells during pluripotency transition. Nucleic Acids Res. 2024 Aug 12;52(14):8146-64. DOI: 10.1093/nar/gkae476
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gkae476
  • dc.identifier.issn 0305-1048
  • dc.identifier.uri http://hdl.handle.net/10230/68873
  • dc.language.iso eng
  • dc.publisher Oxford University Press
  • dc.relation.ispartof Nucleic Acids Res. 2024 Aug 12;52(14):8146-64
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/686637
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/964342
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-114080GB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86760-P
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/754422
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/608959
  • dc.rights © The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.other Expressió gènica
  • dc.title The relationship between nanoscale genome organization and gene expression in mouse embryonic stem cells during pluripotency transition
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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