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.

脉管系统是将血液和氧气输送到身体所有组织的重要器官，因此与缺血性疾病、损伤诱导的再生和实体瘤生长的治疗相关。此前，我们证明 ETV2 是心脏、内皮和造血谱系发育的重要转录因子。在这里，我们报告 ETV2 作为放松封闭染色质和调节内皮发育的先驱因子。通过将工程胚胎干细胞分化和重编程模型与多组学技术进行比较，我们证明 ETV2 能够结合核小体 DNA 并招募 BRG1。BRG1 募集重塑了内皮基因周围的染色质并有助于维持开放构型，从而导致 H3K27ac 沉积增加。总的来说，这些结果将作为开发针对心血管疾病和实体瘤的治疗方案的平台。