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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 01, 2008 |
| Title |
Genome-wide coactivation screen identifies BAF60a as a regulator of lipid metabolism through PGC-1alpha |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Impaired mitochondrial function has been implicated in the pathogenesis of type 2 diabetes, heart failure and neurodegeneration as well as during aging. Studies with the PGC-1 transcriptional coactivators have demonstrated that these factors are key components of the regulatory network that controls mitochondrial function in mammalian cells. Here we describe a genome-wide coactivation assay to globally identify the transcriptional partners for PGC-1α. These analyses revealed a molecular signature of the PGC-1α transcriptional network, and identified BAF60a (Smarcd1), a subunit of the SWI/SNF chromatin-remodeling complex, as a critical regulator of lipid homeostasis. Adenoviral-mediated expression of BAF60a stimulates fatty acid β-oxidation in cultured hepatocytes and reduces hepatic triglyceride levels in diet-induced obese mice. BAF60a physically interacts with PGC-1α and is recruited to PPARα target genes in the fasted liver. Liver-specific RNAi knockdown of BAF60a impairs fatty acid oxidation and results in severe hepatic steatosis following starvation. These results define a role for the SWI/SNF complexes in the regulation of hepatic lipid metabolism, and reveal a potential target for therapeutic intervention.
Keywords: Adenoviral transduction.
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| Overall design |
Primary hepatocytes were isolated from C57/Bl6J mice (10 weeks old) and transduced with recombinant adenoviruses expressing GFP or BAF60a for 40 hrs. Total RNA was isolated for array analysis.
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| Contributor(s) |
Li S, Liu C, Li N, Hao T, Han T, Hill D, Vidal M, Lin J |
| Citation(s) |
18680712 |
| Submission date |
Nov 05, 2007 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Siming Li |
| Organization name |
University of Michigan
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| Street address |
210 Washtenaw Ave
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| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA103329 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE9523_RAW.tar |
12.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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