BAF200 is required for heart morphogenesis and coronary artery development.

BAF200 is required for heart morphogenesis and coronary artery development.
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BAF200 是心脏形态发生和冠状动脉发育所必需的

DOI:
10.1371/journal.pone.0109493
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Zhou B
Zhou B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
He L;Tian X;Zhang H;Hu T;Huang X;Zhang L;Wang Z;Zhou B

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依赖于ATP的SWI/SNF染色质重塑复合体利用ATP水解物以非共价方式改变核小体-DNA相互作用,在干细胞发育、器官发生和肿瘤发生中是必不可少的。生化研究表明,哺乳动物细胞中的SWI/SNF根据亚基组成可分为BAF和PBAF两个亚复合体。ARID2或BAF200被定义为PBAF复合体的固有亚单位。然而,BAF200在体内的功能尚不清楚。为了剖析BAF200在调节胚胎发育和器官发育中的可能作用,我们培育了BAF200突变小鼠,发现它们是胚胎致死的。BAF200突变胚胎在E14.5附近表现出多种心脏缺陷,包括心肌变薄、室间隔缺陷、共同房室瓣和右室双出口。此外,我们还在BAF200突变体中检测到心肌内冠状动脉减少,这表明BAF200对于心外膜下静脉细胞向动脉内皮细胞的正确迁移和分化是必需的。我们的工作表明,PBAF复合体在心脏形态发生和冠状动脉血管生成中起着关键作用。
ATP-dependent SWI/SNF chromatin remodeling complexes utilize ATP hydrolysis to non-covalently change nucleosome-DNA interactions and are essential in stem cell development, organogenesis, and tumorigenesis. Biochemical studies show that SWI/SNF in mammalian cells can be divided into two subcomplexes BAF and PBAF based on the subunit composition. ARID2 or BAF200 has been defined as an intrinsic subunit of PBAF complex. However, the function of BAF200 in vivo is not clear. To dissect the possible role of BAF200 in regulating embryogenesis and organ development, we generated BAF200 mutant mice and found they were embryonic lethal. BAF200 mutant embryos exhibited multiple cardiac defects including thin myocardium, ventricular septum defect, common atrioventricular valve, and double outlet right ventricle around E14.5. Moreover, we also detected reduced intramyocardial coronary arteries in BAF200 mutants, suggesting that BAF200 is required for proper migration and differentiation of subepicardial venous cells into arterial endothelial cells. Our work revealed that PBAF complex plays a critical role in heart morphogenesis and coronary artery angiogenesis.
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