Essential Roles of Cohesin STAG2 in Mouse Embryonic Development and Adult Tissue Homeostasis.

Autor:	De Koninck M; Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain., Lapi E; Epithelial Carcinogenesis Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; CIBERONC, Madrid, Spain., Badía-Careaga C; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain., Cossío I; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain., Giménez-Llorente D; Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain., Rodríguez-Corsino M; Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain., Andrada E; Epithelial Carcinogenesis Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain., Hidalgo A; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain., Manzanares M; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain; Centro de Biología Molecular 'Severo Ochoa' (CBMSO), CSIC-UAM, 28049 Madrid, Spain., Real FX; Epithelial Carcinogenesis Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; CIBERONC, Madrid, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain., Losada A; Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain. Electronic address: alosada@cnio.es.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Aug 11; Vol. 32 (6), pp. 108014.
DOI:	10.1016/j.celrep.2020.108014
Abstrakt:	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. Competing Interests: Declaration of Interests The authors declare no competing interests (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu