BioProject

Vascular endothelial cells upregulate the Notch ligand Jagged1 in response to inflammatory activation. More...

Vascular endothelial cells upregulate the Notch ligand Jagged1 in response to inflammatory activation. Here we show that abrogation of endothelial Notch1 signaling impairs induction of key inflammatory target genes. Accordingly, inducible endothelial-targeted knockout of the canonical Notch transcription factor RBPJ reduces inflammation in a murine model of contact hypersensitivity, while overexpression of constitutive active Notch1 has the opposite effect. We show that the proinflammatory role of Notch1 can be attributed to direct genomic priming of the inflammatory landscape involving crosstalk with NF-κB/RelA and selective activation of enhancers associated with Notch-dependent inflammatory genes. This is the first evidence that canonical Notch signaling supports endothelial activation in response to inflammatory cytokines on the chromatin level. Overall design: Examination of Notch1, RBPJ, NF-κB/RelA, H3K27ac genomic localization by ChIP-seq, in unstimulated and ILβ1-stimulated human umbilical vein endothelial cells (HUVECs) with and without Notch1 knockdown Less...