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- W2112348715 endingPage "1474" @default.
- W2112348715 startingPage "1458" @default.
- W2112348715 abstract "The process whereby the primitive vascular network develops into the mature vasculature, known as angiogenic vascular remodeling, is controlled by the Notch signaling pathway. Of the two mammalian Notch receptors expressed in vascular endothelium, Notch1 is broadly expressed in diverse cell types, whereas Notch4 is preferentially expressed in endothelial cells. As mechanisms that confer Notch4 expression were unknown, we investigated how NOTCH4 transcription is regulated in human endothelial cells and in transgenic mice. The NOTCH4 promoter and the 5′ portion of NOTCH4 assembled into an endothelial cell-specific histone modification pattern. Analysis of NOTCH4 primary transcripts in human umbilical vein endothelial cells by RNA fluorescence in situ hybridization revealed that 36% of the cells transcribed one or both NOTCH4 alleles. The NOTCH4 promoter was sufficient to confer endothelial cell-specific transcription in transfection assays, but intron 1 or upstream sequences were required for expression in the vasculature of transgenic mouse embryos. Cell-type-specific activator protein 1 (AP-1) complexes occupied NOTCH4 chromatin and conferred endothelial cell-specific transcription. Vascular angiogenic factors activated AP-1 and reprogrammed the endogenous NOTCH4 gene in HeLa cells from a repressed to a transcriptionally active state. These results reveal an AP-1-Notch4 pathway, which we propose to be crucial for transducing angiogenic signals and to be deregulated upon aberrant signal transduction in cancer." @default.
- W2112348715 created "2016-06-24" @default.
- W2112348715 creator A5013863229 @default.
- W2112348715 creator A5023433176 @default.
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- W2112348715 creator A5081017740 @default.
- W2112348715 creator A5086828967 @default.
- W2112348715 creator A5088062381 @default.
- W2112348715 date "2005-02-01" @default.
- W2112348715 modified "2023-10-02" @default.
- W2112348715 title "Molecular Determinants of <i>NOTCH4</i> Transcription in Vascular Endothelium" @default.
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