Mesoscale modeling and single-nucleosome tracking reveal remodeling of clutch folding and dynamics in stem cell differentiation

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• dc.contributor.author Gómez García, Pablo
• dc.contributor.author Portilllo-Ledesma, Stephanie
• dc.contributor.author Neguembor, Maria Victoria
• dc.contributor.author Pesaresi, Martina
• dc.contributor.author Oweis, Walaa
• dc.contributor.author Rohrlich, Talia
• dc.contributor.author Wieser, Stefan
• dc.contributor.author Meshorer, Eran
• dc.contributor.author Schlick, Tamar
• dc.contributor.author Cosma, Maria Pia
• dc.contributor.author Lakadamyali, Melike
• dc.date.accessioned 2021-03-17T09:56:29Z
• dc.date.available 2021-03-17T09:56:29Z
• dc.date.issued 2021
• dc.description.abstract Nucleosomes form heterogeneous groups in vivo, named clutches. Clutches are smaller and less dense in mouse embryonic stem cells (ESCs) compared to neural progenitor cells (NPCs). Using coarse-grained modeling of the pluripotency Pou5f1 gene, we show that the genome-wide clutch differences between ESCs and NPCs can be reproduced at a single gene locus. Larger clutch formation in NPCs is associated with changes in the compaction and internucleosome contact probability of the Pou5f1 fiber. Using single-molecule tracking (SMT), we further show that the core histone protein H2B is dynamic, and its local mobility relates to the structural features of the chromatin fiber. H2B is less stable and explores larger areas in ESCs compared to NPCs. The amount of linker histone H1 critically affects local H2B dynamics. Our results have important implications for how nucleosome organization and H2B dynamics contribute to regulate gene activity and cell identity.
• dc.description.sponsorship This work was supported by a University of Pennsylvania Epigenetics Pilot Award (M.L.); an NSF Center for Engineering and Mechanobiology (CEMB) Pilot Award (M.L.); a Linda Pechenik Montague Investigator Award (M.L.); the European Union’s Horizon 2020 Research and Innovation Programme (CellViewer grant 686637 to M.L., M.P.C., and E.M.); Ministerio de Ciencia, Innovación y Universidades ( BFU2017-86760-P [AEI/FEDER, UE]) and Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya (AGAUR grant 2017 SGR 689 to M.P.C.); National NSFC grant 319711771003712 (M.P.C.); National Institutes of Health , National Institute of General Medical Sciences awards R01-GM055264 and R35-GM122562 ; People Program (Marie Curie Actions) FP7/2007–2013 under REA grant 608959 (M.V.N.); and Juan de la Cierva-Incorporación 2017 (M.V.N.)
• dc.format.mimetype application/pdf
• dc.identifier.citation Gómez-García PA, Portillo-Ledesma S, Neguemborg MV, Pesaresi M, Oweis W, Rohrlich T et al. Mesoscale modeling and single-nucleosome tracking reveal remodeling of clutch folding and dynamics in stem cell differentiation. Cell Rep. 2021 Jan 12;34(2):108614. DOI: 10.1016/j.celrep.2020.108614
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2020.108614
• dc.identifier.issn 2211-1247
• dc.identifier.uri http://hdl.handle.net/10230/46820
• dc.language.iso eng
• dc.publisher Science Direct
• dc.relation.ispartof Cell Reports. 2021 Jan 12;34(2):108614
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/686637
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/608959
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86760-P
• dc.rights © 2020 Pablo Aurelio Gómez-García et al. Under a Creative Commons license
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.other Genètica
• dc.subject.other Genòmica
• dc.subject.other Cèl·lules mare
• dc.title Mesoscale modeling and single-nucleosome tracking reveal remodeling of clutch folding and dynamics in stem cell differentiation
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion