RUNX3-ERG Cooperation Orchestrates Endothelial Gene Regulation and Vascular Homeostasis.

Endothelial-specific RUNX3 knockout mice show hypersprouting retinal angiogenesis with reduced DLL4 expression and impaired vascular integrity, including lower VE-cadherin and claudin-5.

• Why it matters: Transcriptional control is essential for vessel stability, yet RUNX3’s endothelial role is unknown, limiting understanding of how dysregulation contributes to pathological angiogenesis and vascular malformations.
• What they did: The study used endothelial RUNX3 knockout mice with postnatal retinal angiogenesis and oxygen-induced retinopathy, plus chromatin accessibility, ChIP-qPCR, and protein interaction assays to test RUNX3–ERG cooperation at ETS:RUNX motifs.
• The result: RUNX3 cooperated with ERG and chromatin regulators to activate CDH5, CLDN5, and DLL4 while repressing ICAM1, and its loss aggravated pathological neovascularization and leukocyte infiltration.

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