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| Status |
Public on Aug 29, 2018 |
| Title |
Inhibition of endothelial Notch signaling attenuates inflammation [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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.
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| 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
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| Contributor(s) |
la Cour Poulsen L, Jetne Edelmann R, Krüger S, Diegues-Hurtado R, Shah A, Espen Stav-Noraas T, Renzi A, Szymanska M, Wang J, Ehling M, Benedito R, Kasprzycka M, Bækkevold E, Sundnes O, Donaldson I, Midwood K, Scott H, Collas P, Siebel CW, Adams RH, Haraldsen G, Sundlisæter E, Hol J |
| Citation(s) |
29449332 |
| Submission date |
Oct 03, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Guttorm Haraldsen |
| E-mail(s) |
guttorm.haraldsen@rr-research.no
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| Organization name |
Oslo University Hospital
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| Department |
Department for Pathology
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| Lab |
LIIPAT
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| Street address |
Sognsvannsveien 20
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| City |
OSLO |
| State/province |
OSLO |
| ZIP/Postal code |
0027 |
| Country |
Norway |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (15)
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| This SubSeries is part of SuperSeries: |
| GSE85987 |
Inhibition of endothelial Notch signaling attenuates inflammation |
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| Relations |
| BioProject |
PRJNA345175 |
| SRA |
SRP090746 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE87552_RAW.tar |
2.9 Gb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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