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EP300/NCOA1 complex drives glioma angiogenesis via H3K27 acetylation-dependent activation of VEGFA
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DOI：10.1016/j.yexcr.2026.115004.png)
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Abstract
En 中文
Angiogenesis is essential for glioma progression, yet the epigenetic mechanisms driving this process remain incompletely defined. In this study, we investigated the role of the histone acetyltransferase EP300 in regulating VEGFA expression and promoting endothelial activation. Using glioma cell lines with EP300 overexpression or knockdown, we found that EP300 markedly enhanced endothelial proliferation, invasion, and tube formation, while its silencing produced opposite effects. Mechanistic analyses revealed that EP300 increased H3K27 acetylation at the VEGFA promoter, thereby activating VEGFA transcription. Pharmacologic blockade of EP300 activity or VEGFA neutralization abolished these pro-angiogenic effects. Through integrative analysis of TCGA data and protein complex databases, NCOA1 was identified as a key EP300-associated cofactor. Coimmunoprecipitation and nuclear-cytoplasmic assays confirmed that EP300 forms a nuclear transcriptional coactivator complex with NCOA1, which stabilizes its nuclear localization and synergistically enhances VEGFA expression. Together, these findings identify EP300 as a central epigenetic regulator of glioma angiogenesis and highlight the EP300/NCOA1-VEGFA axis as a potential therapeutic target.
Keywords:
EP300
Angiogenesis
Glioma
Histone acetylation
Molecular mechanism
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