The histone lysine methyltransferase SETD8 regulates angiogenesis through HES-1 in human umbilical vein endothelial cells.

Scientific Reports
Dong Kyu ChoiJi Hoon Yu

Abstract

Histone modifications, including histone lysine methylation, regulate gene expression in the vasculature, and targeting tumor blood vessels through histone modification decreases tumor growth. SETD8, a methyltransferase that catalyzes the mono-methylation of histone H4 lysine 20 is known to promote tumorigenesis in various cancers and its high levels of expression are related to poor prognosis. However, the detailed mechanisms by which SETD8 stimulates tumor progression and angiogenesis are still not well understood. Recent studies have demonstrated that, in vitro, BVT-948 efficiently and selectively suppresses SETD8 activity and histone methylation levels. In this study, we showed that BVT-948-mediated SETD8 inhibition in HUVECs results in an inhibition of angiogenesis. Inhibition of SETD8 not only inhibited angiogenesis but also disrupted actin stress fiber formation and induced cell cycle arrest at S phase. These effects were accompanied by increased HES-1 expression levels, decreased osteopontin levels, and a decreased differentiation of human induced pluripotent stem cells into endothelial cells. Interestingly, BVT-948 treatment reduced pathological angiogenesis in mouse OIR model. These data illustrate the mechanisms by w...Continue Reading

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Datasets Mentioned

BETA
AB5320

Methods Mentioned

BETA
ubiquitination
PCR
GTPase
flow cytometry
FACS

Software Mentioned

GraphPad
Incucyte ZOOM
Prism
FlowJo

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