|
| Status |
Public on Feb 04, 2016 |
| Title |
Differential gene expression following MafG overexpression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR
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| Overall design |
Wild-type C57BL/6 mice were treated with either Ad-Control (Ad-CMV) or Ad-MafG for 5 days. Livers were then harvested following a 4-6h fast, RNA was isolated and analyzed by Illumina Microarray.
6 samples were analyzed, 3 per condition. Each sample represents one mouse.
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| Contributor(s) |
de Aguiar Vallim T, Edwards PA |
| Citation(s) |
25651182 |
| |
| Submission date |
Feb 02, 2016 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Thomas A Vallim |
| E-mail(s) |
tvallim@mednet.ucla.edu
|
| Organization name |
UCLA
|
| Street address |
650 Charles E. Young Drive South, A2-237 CHS
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 (MC 167917) |
| Country |
USA |
| |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE77559 |
MAFG is a transcriptional repressor of bile acid synthesis and metabolism |
|
| Relations |
| BioProject |
PRJNA310734 |
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