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| Status |
Public on Feb 26, 2020 |
| Title |
H3K27Ac ChIP-Seq in Prdm16 KO duodenal crypts |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The adult intestinal epithelium is maintained by a continuous replacement of differentiated cells from stem cells. Previous studies suggest that cellular metabolic pathways regulate intestinal stem cell activity and differentiation. However, little is known about the cell-intrinsic factors that control these metabolic programs. Here, we identify the transcription factor PRDM16 as a critical regulator of intestinal metabolic programing and stem cell differentiation. Acute deletion of Prdm16 in adult mice causes severe intestinal wasting, apoptosis, and an accumulation of poorly differentiated cells in the crypt. Prdm16-deficient crypts display decreased expression levels of fatty acid oxidation (FAO) genes and reduced rates of FAO. PRDM16 binds, along with its protein partners PPAR? and PPAR?, to the promoter and enhancer regions of many FAO genes. The loss of Prdm16 or inhibition of FAO impaired the transition of intestinal stem cells into transit amplifying cells. Notably, PRDM16 expression is highest in the duodenum and declines distally along the intestine. This gradient of PRDM16 expression controls the region-specific expression of the FAO program and underlies the differential reliance of region-specific stem cells on FAO. Altogether, this study establishes PRDM16 as a regional-specific regulator of metabolism and stem cell differentiation in the intestine.
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| Overall design |
H3K27Ac was performed on control and Prdm16 KO crypts isolated from the duodenum of 6 week old mice injected with tamoxifen 3 days before crypt extraction
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| Contributor(s) |
Seale P, Stine RR |
| Citation(s) |
31564549 |
| Submission date |
Oct 05, 2018 |
| Last update date |
Feb 26, 2020 |
| Contact name |
Patrick Seale |
| Organization name |
University of Pennsylvania
|
| Department |
Institute for Diabetes, Obesity & Metabolism
|
| Street address |
Smilow Center for Translational Research, 12th Floor 3400 Civic Center Blvd. Bldg 421
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE121014 |
Control of region-specific intestinal metabolism and maintenance by PRDM16 |
|
| Relations |
| BioProject |
PRJNA494860 |
| SRA |
SRP163675 |
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