SMARCAD1 and TOPBP1 contribute to heterochromatin maintenance at the transition from the 2C-like to the pluripotent state

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• dc.contributor.author Sebastián Pérez, Rubén
• dc.contributor.author Nakagawa, Shoma
• dc.contributor.author Tu, Xiaochuan
• dc.contributor.author Aranda Aragón, Sergio
• dc.contributor.author Pesaresi, Martina
• dc.contributor.author Gómez García, Pablo
• dc.contributor.author Alcoverro-Bertran, Marc
• dc.contributor.author Gómez Vázquez, José Luis
• dc.contributor.author Carnevali, Davide
• dc.contributor.author Borràs, Eva
• dc.contributor.author Sabidó Aguadé, Eduard, 1981-
• dc.contributor.author Martin, Laura
• dc.contributor.author Nissim Rafinia, Malka
• dc.contributor.author Meshorer, Eran
• dc.contributor.author Neguembor, Maria Victoria
• dc.contributor.author Di Croce, Luciano
• dc.contributor.author Cosma, Maria Pia
• dc.date.accessioned 2023-11-06T07:42:00Z
• dc.date.available 2023-11-06T07:42:00Z
• dc.date.issued 2023
• dc.description.abstract Chromocenters are established after the 2-cell (2C) stage during mouse embryonic development, but the factors that mediate chromocenter formation remain largely unknown. To identify regulators of 2C heterochromatin establishment, we generated an inducible system to convert embryonic stem cells (ESCs) to 2C-like cells. This conversion is marked by a global reorganization and dispersion of H3K9me3-heterochromatin foci, which are then reversibly formed upon re-entry into pluripotency. Profiling the chromatin-bound proteome (chromatome) by genome capture of ESCs transitioning to 2C-like cells, we uncover chromatin regulators involved in de novo heterochromatin formation. We identified TOPBP1 and investigated its binding partner SMARCAD1. SMARCAD1 and TOPBP1 associate with H3K9me3-heterochromatin in ESCs. Interestingly, the nuclear localization of SMARCAD1 is lost in 2C-like cells. SMARCAD1 or TOPBP1 depletion in mouse embryos lead to developmental arrest, reduction of H3K9me3 and remodeling of heterochromatin foci. Collectively, our findings contribute to comprehending the maintenance of chromocenters during early development.
• dc.description.sponsorship This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme (CellViewer No 686637 to M.P.C.); Ministerio de Ciencia e Innovación, grant BFU2017-86760-P (AEI/FEDER, UE); and an AGAUR grant from Secretaria d’Universitats i Recerca del Departament d’Empresa I Coneixement de la Generalitat de Catalunya (2017 SGR 689 to M.P.C.); National Natural Science Foundation of China (No 31971177 to M.P.C.); Spanish Ministry of Economy, Industry and Competitiveness (MEIC) (PID2019-108322GB-100 to L.D.C.), and from AGAUR (L.D.C.). We acknowledge the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme. The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and it is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I+D+i 2013-2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF. R.S.-P. was supported by a FI-AGAUR PhD fellowship from the Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya and the co-finance of Fondo Social Europeo (2018FI_B_00637 and FSE). X.T. is supported by a FPI PhD fellowship from the Ministerio de Ciencia e Innovación (PRE2018-085107). S.A. is funded by the Ramon y Cajal program of the Ministerio de Ciencia, Innovación y Universidades and the European Social Fund under the reference number RYC-2018-025002-I, and the Instituto de Salud Carlos III-FEDER (PI19/01814). L.M. is supported by a 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) and La Caixa Foundation fellowship (LCF/BQ/DR20/11790016). M.P. was supported by a Severo Ochoa PhD fellowship from the Subprograma Estatal de Formación del Ministerio de Economía y Competitividad (BES-2015-072802). M.V.N. is funded by FP7/2007–2013 under an REA grant (608959) and Juan de la Cierva-Incorporación 2017.
• dc.format.mimetype application/pdf
• dc.identifier.citation Ruben Sebastian-Perez R, Nakagawa S, Tu X, Aranda S, Pesaresi M, Gomez-Garcia PA, Alcoverro-Bertran M, Gomez-Vazquez JL, Carnevali D, Borràs E, Sabidó E, Martin L, Nissim-Rafinia M, Meshorer E, Neguembor MV, Di Croce L, Cosma MP. SMARCAD1 and TOPBP1 contribute to heterochromatin maintenance at the transition from the 2C-like to the pluripotent state. eLife. 2023;12:RP87742. DOI: 10.7554/eLife.87742.1
• dc.identifier.doi http://dx.doi.org/10.7554/eLife.87742.1
• dc.identifier.issn 2050-084X
• dc.identifier.uri http://hdl.handle.net/10230/58213
• dc.language.iso eng
• dc.publisher eLife
• dc.relation.ispartof eLife. 2023;12:RP87742
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/686637
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86760-P
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-108322GB-100
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/608959
• dc.rights © 2023, Sebastian-Perez et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Cromosomes
• dc.subject.other Cromatina
• dc.subject.other Genètica
• dc.title SMARCAD1 and TOPBP1 contribute to heterochromatin maintenance at the transition from the 2C-like to the pluripotent state
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion