Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

OBJECTIVE: Endothelial upregulation of adhesion molecules serves to recruit leukocytes to inflammatory sites and appears to be promoted by NOTCH1; however, current models based on interactions between active NOTCH1 and NF-κB components cannot explain the transcriptional selectivity exerted by NOTCH1 in this context. APPROACH AND RESULTS: Observing that Cre/Lox-induced conditional mutations of endothelial Notch modulated inflammation in murine contact hypersensitivity, we found that IL (interleukin)-1β stimulation induced rapid recruitment of RELA (v-rel avian reticuloendotheliosis viral oncogene homolog A) to genomic sites occupied by NOTCH1-RBPJ (recombination signal-binding protein for immunoglobulin kappa J region) and that NOTCH1 knockdown reduced histone H3K27 acetylation at a subset of NF-κB-directed inflammatory enhancers. CONCLUSIONS: Our findings reveal that NOTCH1 signaling supports the expression of a subset of inflammatory genes at the enhancer level and demonstrate how key signaling pathways converge on chromatin to coordinate the transition to an infla mmatory endothelial phenotype.

Original publication




Journal article


Arterioscler thromb vasc biol

Publication Date





854 - 869


animals, endothelial cells, inflammation, mice, mutation, Acetylation, Animals, Appendicitis, Cells, Cultured, Dermatitis, Contact, Dipeptides, Disease Models, Animal, Endothelial Cells, Female, Gene Expression Regulation, Histones, Human Umbilical Vein Endothelial Cells, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Inflammation, Interleukin-1beta, Male, Mice, Inbred C57BL, Mice, Transgenic, Phenotype, Receptor, Notch1, Signal Transduction, Transcription Factor RelA