重编程
转录因子
染色质
生物
细胞生物学
胚胎干细胞
造血
染色质重塑
再生(生物学)
干细胞
免疫学
遗传学
基因
细胞
作者
Wuming Gong,Satyabrata Das,Javier E. Sierra-Pagán,Erik Skie,Nikita Dsouza,Thijs A Larson,Mary G. Garry,Edgar Luzete-Monteiro,Kenneth S. Zaret,Daniel J. Garry
标识
DOI:10.1038/s41556-022-00901-3
摘要
The vasculature is an essential organ for the delivery of blood and oxygen to all tissues of the body and is thus relevant to the treatment of ischaemic diseases, injury-induced regeneration and solid tumour growth. Previously, we demonstrated that ETV2 is an essential transcription factor for the development of cardiac, endothelial and haematopoietic lineages. Here we report that ETV2 functions as a pioneer factor that relaxes closed chromatin and regulates endothelial development. By comparing engineered embryonic stem cell differentiation and reprogramming models with multi-omics techniques, we demonstrated that ETV2 was able to bind nucleosomal DNA and recruit BRG1. BRG1 recruitment remodelled chromatin around endothelial genes and helped to maintain an open configuration, resulting in increased H3K27ac deposition. Collectively, these results will serve as a platform for the development of therapeutic initiatives directed towards cardiovascular diseases and solid tumours.
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