 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 01, 2020 |
| Title |
SETDB1 safeguards genome stability against necroptosis and bowel inflammation (ChIP-seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The aetiology of bowel inflammatory disease (IBD) is a multifactorial interplay between heredity and environment1-3. Here we report SETDB1, a histone methyltransferase (HMTs) for histone H3 lysine 9 trimethylation (H3K9me3) whose deficiency participates in the pathogenesis of IBD. We found that SETDB1 level decreased in IBD patients and that mice with reduced SETDB1 in intestinal stem cells (ISCs) developed spontaneous terminal ileitis and colitis. SETDB1 safeguards genome stability4, of which the loss in ISCs released repression of endogenous retrovirus (ERVs), the retrovirus-like elements with long repeats that comprise ~8% of genome5. Excessive viral mimicry generated by motivated ERVs triggered Z-DNA-binding protein 1 (ZBP1) dependent necroptosis, which irreversibly disrupted the homeostasis of epithelial barrier and promoted bowel inflammation. Of note, genome instability, reactive ERVs, upregulation of ZBP1 and necroptosis were seen in IBD patients. Pharmaceutic inhibition of RIP3 showed curative effect in SETDB1 deficient mice, suggesting therapy targeting ISC necroptosis may represent a new approach for severe IBD treatment.
|
| |
|
| Overall design |
Examination of H3K9me3 in intestinal stem cell.
|
| |
|
| Contributor(s) |
Li H, wang r |
| Citation(s) |
32296174 |
| Submission date |
Apr 02, 2019 |
| Last update date |
Apr 21, 2020 |
| Contact name |
hongda li |
| E-mail(s) |
lihongda91@163.com
|
| Organization name |
Xiamen University
|
| Street address |
School of Life Sciences, Xiang'an Campus, Xiamen University, Xiang'an District, Xiamen, Fujian Province, China
|
| City |
xiamen |
| ZIP/Postal code |
361102 |
| Country |
China |
| |
|
| Platforms (1) |
|
| Samples (2) |
|
| This SubSeries is part of SuperSeries: |
| GSE129174 |
Setdb1 safeguards genome stability against stem cell necroptosis and bowel inflammation |
|
| Relations |
| BioProject |
PRJNA530394 |
| SRA |
SRP190123 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE129173_RAW.tar |
660.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
