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Status |
Public on Feb 04, 2016 |
Title |
MAFG is a transcriptional repressor of bile acid synthesis and metabolism (ChIP-seq) |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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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 |
ChIP-Seq analysis for livers overexpressing BLRP-tagged MafG and BLRP control
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Contributor(s) |
de Aguiar Vallim T, Romanoski C |
Citation(s) |
25651182 |
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Submission date |
Feb 03, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Thomas A Vallim |
E-mail(s) |
tvallim@mednet.ucla.edu
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Organization name |
UCLA
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Street address |
650 Charles E. Young Drive South, A2-237 CHS
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City |
Los Angeles |
State/province |
CA |
ZIP/Postal code |
90095 (MC 167917) |
Country |
USA |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (4)
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This SubSeries is part of SuperSeries: |
GSE77559 |
MAFG is a transcriptional repressor of bile acid synthesis and metabolism |
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Relations |
BioProject |
PRJNA310736 |
SRA |
SRP069237 |