BioProject

STAG2 is commonly mutated in cancer and germline mutations have been identified in cohesinopathy patients. More...

STAG2 is commonly mutated in cancer and germline mutations have been identified in cohesinopathy patients. To better understand the underlying pathogenic mechanisms, we here 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 showing global developmental delay and defective heart morphogenesis, most prominently in structures derived from secondary heart field progenitors. Our analyses suggest that both decreased proliferation and altered transcription of tissue-specific genes contribute to these defects. These results provide compelling evidence on cell- and tissue-specific roles of the two cohesin complexes and how their dysfunction contributes to disease. Overall design: RNA-Seq for STAG2 KO and WT embryos at E9.5 (21-23 pairs of somites) Less...