2024-03-29T01:32:59Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/109802023-08-31T06:27:17Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
00925njm 22002777a 4500
dc
Lapi, Eleonora
author
Badia-Careaga, Claudio
author
Cossío, Itziar
author
Giménez-Llorente, Daniel
author
Rodríguez-Corsino, Miriam
author
Andrada, Elena
author
Hidalgo, Andres
author
Manzanares, Miguel
author
Real Arribas, Francisco
author
Losada, Ana
author
De Koninck, Magali
author
2020-08-11
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.
Cell Rep . 2020;32(6):108014.
http://hdl.handle.net/20.500.12105/10980
32783938
10.1016/j.celrep.2020.108014
2211-1247
Cell reports
GENE-EXPRESSION
BLADDER-CANCER
MUTATIONS
MICE
P16(INK4A)
DEFICIENCY
DELETION
TRACT
LEADS
Essential Roles of Cohesin STAG2 in Mouse Embryonic Development and Adult Tissue Homeostasis.