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Updated: Dec 29, 2025
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A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
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Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis
Jiahuan Chen1, Xiaodong Liang1, Shasha Zhang1
1Department of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
Cell Death & Disease
|February 1, 2020
Summary
Bivalent domains (BDs) in endothelial cells control vascular endothelial growth factor A (VEGFA) response. EZH1 promotes angiogenesis via EGR3, while KDM5A dampens it, revealing BDs
Area of Science:
- Epigenetics
- Molecular Biology
- Developmental Biology
Background:
- Bivalent domains (BDs) are epigenetic marks found at gene promoters, crucial for cell differentiation in embryonic stem cells.
- The role of BDs in differentiated cells, particularly endothelial cells, was previously unclear.
Purpose of the Study:
- To investigate the function and characteristics of BDs in endothelial cells during vascular endothelial growth factor A (VEGFA) stimulation.
- To elucidate the mechanisms regulating the expression of VEGFA-responsive genes marked by BDs.
- To determine the impact of BDs on angiogenesis.
Main Methods:
- Profiling the epigenetic landscape of endothelial cells.
- Analyzing gene expression changes in response to VEGFA stimulation.
- Investigating the roles of EZH1 and KDM5A in regulating bivalent gene expression and angiogenesis.
Main Results:
- BDs are prevalent in endothelial cells and are enriched at VEGFA-responsive genes, exhibiting a more permissive chromatin state.
- VEGFA-induced gene activation involves EZH1-mediated release of RNA Polymerase II (RNAPII) pausing, not H3K27me3 removal.
- Gene suppression relies on KDM5A recruitment by Polycomb Repressive Complex 2 (PRC2), and EZH1 promotes, while KDM5A inhibits, angiogenesis.
Conclusions:
- BDs play a dual role in endothelial cells, modulating VEGFA responsiveness and angiogenesis.
- EZH1 and KDM5A act antagonistically to control angiogenesis through epigenetic regulation of bivalent genes.
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