Endothelial-specific YY1 governs sprouting angiogenesis through directly interacting with RBPJ

Area of Science:

• Molecular Biology
• Developmental Biology
• Vascular Biology

Background:

• Angiogenesis, the formation of new blood vessels, is a complex process regulated by gene transcription.
• Yin Ying 1 (YY1) is a transcription factor with known diverse functions, but its specific role in vascular development is unclear.

Purpose of the Study:

• To investigate the cell-type-specific function of the transcription factor Yin Ying 1 (YY1) in endothelial cells during angiogenesis and vascular development.

Main Methods:

• Generated tamoxifen-inducible endothelial cell-specific YY1 knockout mice.
• Utilized mouse retinal sprouting angiogenesis assays, ex vivo mouse aortic ring assays, and human endothelial cell culture.
• Investigated the molecular mechanism involving Notch signaling pathway components RBPJ and MAML1.

Main Results:

• Endothelial cell-specific deletion of YY1 resulted in embryonic lethality due to severe defects in angiogenesis and vascular formation.
• YY1 deficiency led to reduced retinal sprouting angiogenesis, fewer tip cells, and impaired vessel maturation.
• YY1 acts as a repressor of Notch signaling by competing with MAML1 for RBPJ binding, thereby inhibiting the NICD/MAML1/RBPJ complex and promoting tip cell formation.

Conclusions:

• Endothelial YY1 is essential for normal vascular development and sprouting angiogenesis.
• YY1 regulates endothelial tip-stalk fate determination by repressing Notch signaling through direct interaction with RBPJ.
• The YY1-RBPJ complex plays a critical role in controlling angiogenesis.