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Whole-mount Immunohistochemical Analysis for Embryonic Limb Skin Vasculature: a Model System to Study Vascular Branching Morphogenesis in Embryo
Published on: May 20, 2011
BRG1 promotes COUP-TFII expression and venous specification during embryonic vascular development
Reema B Davis1, Carol D Curtis, Courtney T Griffin
1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Development (Cambridge, England)
|February 15, 2013
Summary
The chromatin remodeler BRG1 promotes venous identity by upregulating COUP-TFII expression in endothelial cells. This study reveals a novel role for chromatin remodeling in vascular development and venous specification.
Area of Science:
- Vascular Biology
- Epigenetics
- Developmental Biology
Background:
- Arteries and veins develop distinct molecular identities early in embryonic development.
- The transcription factor COUP-TFII is a key regulator of venous fate, inhibiting arterialization.
- The upstream regulation of COUP-TFII in veins remains largely unknown.
Purpose of the Study:
- To identify factors regulating COUP-TFII expression in venous endothelial cells.
- To elucidate the role of chromatin remodeling in venous specification.
Main Methods:
- Conditional deletion of the Brg1 gene in murine vascular endothelial cells.
- Analysis of COUP-TFII expression and arterial/venous marker expression.
- Chromatin immunoprecipitation and reporter assays to assess promoter binding and activity.
Main Results:
- Conditional deletion of Brg1 downregulated COUP-TFII expression in veins.
- Loss of Brg1 led to aberrant expression of arterial markers on veins.
- BRG1 directly binds to regulatory elements of the COUP-TFII promoter, facilitating chromatin accessibility.
Conclusions:
- The chromatin-remodeling enzyme BRG1 is essential for promoting COUP-TFII expression in venous endothelial cells.
- BRG1-mediated chromatin remodeling plays a novel and critical role in establishing venous identity during development.
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