Essential Roles of Cohesin STAG2 in Mouse Embryonic Development and Adult Tissue Homeostasis
| Autor: | Miriam Rodríguez-Corsino, Ana Losada, Daniel Giménez-Llorente, Andrés Hidalgo, Francisco X. Real, Claudio Badia-Careaga, Magali De Koninck, Itziar Cossío, Miguel Manzanares, Elena Andrada, Eleonora Lapi |
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| Přispěvatelé: | Ministerio de Ciencia e Innovación (España), European Regional Development Fund (ERDF/FEDER), Fundación Científica AECC, Instituto de Salud Carlos III - ISCIII, Fundación ProCNIC, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, European Union (EU), Asociacion Espanola Contra el Cancer (AECC), Severo Ochoa Centers of Excellence, Agencia Estatal de Investigación (España), Fundación Científica Asociación Española Contra el Cáncer |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Heart morphogenesis Somatic cell Chromosomal Proteins Non-Histone BLADDER-CANCER Embryonic Development Cell Cycle Proteins Biology Tissue-specific transcription General Biochemistry Genetics and Molecular Biology Chromosome segregation cohesinopathy 03 medical and health sciences Mice heart morphogenesis 0302 clinical medicine Germline mutation P16(INK4A) Animals Homeostasis cancer lcsh:QH301-705.5 Tissue homeostasis GENE-EXPRESSION Mice Knockout Cohesin MUTATIONS DELETION Embryonic stem cell hematopoiesis Cell biology intestinal tissue homeostasis Establishment of sister chromatid cohesion DEFICIENCY MICE 030104 developmental biology LEADS lcsh:Biology (General) knockout mouse 030217 neurology & neurosurgery TRACT |
| Zdroj: | Cell Reports, Vol 32, Iss 6, Pp 108014-(2020) Repisalud Instituto de Salud Carlos III (ISCIII) Digital.CSIC. Repositorio Institucional del CSIC Universitat Politècnica de Catalunya (UPC) |
| ISSN: | 2211-1247 |
| Popis: | 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.Cells carry STAG1- and STAG2-cohesin complexes whose functional specificity remains unclear. De Koninck et al. show that Stag2 deletion in mice results in embryonic lethality by mid-gestation. In contrast, STAG2 is not strictly required for viability in cells or adult tissues, and its loss is not sufficient to elicit tumorigenesis. 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) |
| Databáze: | OpenAIRE |
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