Essential roles of cohesin STAG2 in mouse embryonic development and adult tissue homeostasis

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  • dc.contributor.author De Koninck, Magali
  • dc.contributor.author Lapi, Eleonora
  • dc.contributor.author Badía Careaga, Claudio
  • dc.contributor.author Cossío, Itziar
  • dc.contributor.author Giménez-Llorente, Daniel
  • dc.contributor.author Rodríguez-Corsino, Miriam
  • dc.contributor.author Andrada, Elena
  • dc.contributor.author Hidalgo, Andrés
  • dc.contributor.author Manzanares, Miguel
  • dc.contributor.author Real, Francisco X.
  • dc.contributor.author Losada, Ana
  • dc.date.accessioned 2020-09-23T06:02:48Z
  • dc.date.available 2020-09-23T06:02:48Z
  • dc.date.issued 2020
  • dc.description.abstract Cohesin mediates sister chromatid cohesion and 3D genome folding. Two versions of the complex carrying STAG1 or STAG2 coexist in somatic vertebrate cells. STAG2 is commonly mutated in cancer, and germline mutations have been identified in cohesinopathy patients. To better understand the underlying pathogenic mechanisms, we report the consequences of Stag2 ablation in mice. STAG2 is largely dispensable in adults, and its tissue-wide inactivation does not lead to tumors but reduces fitness and affects both hematopoiesis and intestinal homeostasis. STAG2 is also dispensable for murine embryonic fibroblasts in vitro. In contrast, Stag2-null embryos die by mid-gestation and show global developmental delay and defective heart morphogenesis, most prominently in structures derived from secondary heart field progenitors. Both decreased proliferation and altered transcription of tissue-specific genes contribute to these defects. Our results provide compelling evidence on cell- and tissue-specific roles of different cohesin complexes and how their dysfunction contributes to disease.
  • dc.description.sponsorship This work has been supported by the State Research Agency (AEI), Spanish Ministry of Science and Innovation, with cofunding of the European Regional Development Funds (grants BFU2013-48481-R and BFU2016-79841-R to A.L., SAF2015-70553-R to F.X.R., BFU2017-84914-P and BFU2015-72319-EXP to M.M., and BES-2014-069166 fellowship to M.D.K.), and a grant to F.X.R. and a Postdoctoral Contract to E.L. from the Fundación Científica de la Asociación Española Contra el Cáncer. Both CNIO and CNIC are supported by Instituto de Salud Carlos III (ISCIII) and Severo Ochoa Centers of Excellence (SEV-2015-0510 and SEV-2015-0505). The CNIC is also supported by the Pro CNIC Foundation.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation De Koninck M, Lapi E, Badía-Careaga C, Cossío I, Giménez-Llorente D, Rodríguez-Corsino M, Andrada E, Hidalgo A, Manzanares M, Real FX, Losada A. Essential roles of cohesin STAG2 in mouse embryonic development and adult tissue homeostasis. Cell Rep. 2020; 32(6):108014. DOI: 10.1016/j.celrep.2020.108014
  • dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2020.108014
  • dc.identifier.issn 2211-1247
  • dc.identifier.uri http://hdl.handle.net/10230/45326
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Cell Rep. 2020; 32(6):108014
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-48481-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016-79841-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-70553-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-84914-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-72319-EXP
  • dc.rights © 2020 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Cancer
  • dc.subject.keyword Chromosome segregation
  • dc.subject.keyword Cohesinopathy
  • dc.subject.keyword Heart morphogenesis
  • dc.subject.keyword Hematopoiesis
  • dc.subject.keyword Intestinal tissue homeostasis
  • dc.subject.keyword Knockout mouse
  • dc.subject.keyword Tissue-specific transcription
  • dc.title Essential roles of cohesin STAG2 in mouse embryonic development and adult tissue homeostasis
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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