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Series GSE9523 Query DataSets for GSE9523
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
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.
 
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.
 
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
Street address 210 Washtenaw Ave
City Ann Arbor
State/province MI
ZIP/Postal code 48109
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (2)
GSM241210 Hepatocyte_BAF60a
GSM241211 Hepatocyte_GFP
Relations
BioProject PRJNA103329

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Supplementary file Size Download File type/resource
GSE9523_RAW.tar 12.4 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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