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| Status |
Public on Feb 27, 2018 |
| Title |
IL-10 signaling remodels adipose chromatin architecture to limit thermogenesis and energy expenditure [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the physiologic limiters of energy expenditure are largely unknown. Here we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and mature adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to cold, obesity and aging. ATAC-seq and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and PGC-1alpha recruitment to key enhancer regions. These findings identify the IL-10 axis as a critical and potentially targetable regulator of thermogenesis, and expand our understanding of the links between inflammatory signaling and adipose tissue function in the setting of obesity.
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| Overall design |
D5 differentiated cells treated with and without IL10. Input served as a control for C/EBPβ enrichment. ChIP-Seq libraries were prepared using the Kapa LTP Library Preparation Kit (Kapa Biosystems). ChIP-Seq was performed as described (Tong et al., 2016).
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| Contributor(s) |
Thomas BJ, Rajbhandari P |
| Citation(s) |
29249357 |
| Submission date |
Feb 27, 2018 |
| Last update date |
Mar 19, 2019 |
| Contact name |
Peter Tontonoz |
| Organization name |
UCLA
|
| Department |
Pathology
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| Lab |
Tontonoz Lab
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| Street address |
675 Charles E Young
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE94654 |
IL-10 signaling remodels adipose chromatin architecture to limit thermogenesis and energy expenditure |
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| Relations |
| BioProject |
PRJNA436164 |
| SRA |
SRP133606 |
