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.
|Original language||English (US)|
|Number of pages||13|
|Journal||Nature Cell Biology|
|State||Published - May 2022|
Bibliographical noteFunding Information:
This work was supported by a grant from the Department of Defense (W81XWH2110606) and Minnesota Regenerative Medicine. We thank N. Koyano, K.-D. Choi and B. N. Singh for technical assistance and discussions. We acknowledge G. R. Crabtree and B. Bruneau for providing the Brg1;ActinCreER ES cells. We acknowledge the University of Minnesota Genomics Center for their technical assistance and the Minnesota Supercomputing Institute for providing computational resources. We recognize C. Faraday for assistance with figure layout and preparation. f/f
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.