ETV2 functions as a pioneer factor to regulate and reprogram the endothelial lineage

Wuming Gong; Satyabrata Das; Javier E. Sierra-Pagan; Erik Skie; Nikita Dsouza; Thijs A. Larson; Mary G. Garry; Edgar Luzete-Monteiro; Kenneth S. Zaret; Daniel J. Garry

doi:10.1038/s41556-022-00901-3

ETV2 functions as a pioneer factor to regulate and reprogram the endothelial lineage

Wuming Gong, Satyabrata Das, Javier E. Sierra-Pagan, Erik Skie, Nikita Dsouza, Thijs A. Larson, Mary G. Garry, Edgar Luzete-Monteiro, Kenneth S. Zaret, Daniel J. Garry

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

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)
Pages (from-to)	672-684
Number of pages	13
Journal	Nature Cell Biology
Volume	24
Issue number	5
DOIs	https://doi.org/10.1038/s41556-022-00901-3
State	Published - May 2022

Bibliographical note

Funding 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

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.

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Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

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abstract = "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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note = "Funding 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 Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",

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AU - Larson, Thijs A.

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AU - Zaret, Kenneth S.

AU - Garry, Daniel J.

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N2 - 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.

AB - 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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ETV2 functions as a pioneer factor to regulate and reprogram the endothelial lineage

Abstract

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