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| Status |
Public on Feb 27, 2017 |
| Title |
Epigenomic rescue of genetically defective Ucp1 expression in subcutaneous fat of C57BL/6 mice [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Obesity causes insulin resistance, and PPARγ ligands like rosiglitazone (rosi) are insulin-sensitizing, yet mechanisms remain unclear. High fat diet (HFD) induced obesity has major effects on visceral epididymal adipose tissue (eWAT) of C57BL/6 (B6) mice, and here we report altered activity of gene regulatory elements with changes in PPARγ genome-wide occupancy. Treatment with rosi restored insulin sensitivity, yet surprisingly had little effect on eWAT, leading us to consider the subcutaneous inguinal fat (iWAT). In this depot, rosi markedly induced molecular signatures of brown fat including the key thermogenic gene Ucp1. Obesity-resistant 129S1/SvImJ (129) mice showed this degree of iWAT browning even in the absence of rosi. Remarkably, the 129 Ucp1 locus had increased PPARγ binding and gene expression that was preserved in B6x129 F1 intercross iWAT, with imbalance favoring the 129-derived alleles showing a cis-acting genetic difference. Thus, B6 mice have a genetic defect in Ucp1 expression. However, imbalanced expression favoring 129 over B6 was nearly lost when Ucp1 was activated by rosi, or by iWAT browning in cold-exposed or young mice. These results provide a novel framework for understanding how environmental influences like drugs can rescue genetically determined disease phenotypes by affecting the epigenome.
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| Overall design |
C57BL/6J and 129S1/SvlmJ mice were on LFD or HFD; then treated with rosiglitazone
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| Contributor(s) |
Soccio R |
| Citation(s) |
28240605 |
| |
| Submission date |
Dec 20, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Raymond Soccio |
| E-mail(s) |
soccio@mail.med.upenn.edu
|
| Organization name |
University of Pennsylvania
|
| Street address |
3400 Civic Center Blvd
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (45)
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| This SubSeries is part of SuperSeries: |
| GSE92607 |
Epigenomic rescue of genetically defective Ucp1 expression in subcutaneous fat of C57BL/6 mice |
|
| Relations |
| BioProject |
PRJNA358148 |
| SRA |
SRP095388 |
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