Transcriptomics

Dataset Information

5

Transcription profiling of mouse primaty hepatocytes reveals a coactivation screen identifies BAF60a as a regulator of lipid metabolism through PGC-1alpha


ABSTRACT: 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. Experiment 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.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Mus Musculus

SUBMITTER: Siming Li 

PROVIDER: E-GEOD-9523 | ArrayExpress | 2008-10-20

SECONDARY ACCESSION(S): GSE9523PRJNA103329

REPOSITORIES: GEO, ArrayExpress

Dataset's files

Source:
Action DRS
E-GEOD-9523.README.txt Txt
E-GEOD-9523.eSet.r Other
E-GEOD-9523.idf.txt Idf
E-GEOD-9523.processed.1.zip Processed
E-GEOD-9523.raw.1.zip Raw
Items per page:
1 - 5 of 6

Similar Datasets

2008-08-01 | GSE9523 | GEO
| E-GEOD-9523 | BioStudies
| S-EPMC2578827 | BioStudies
| S-EPMC7424056 | BioStudies
| S-EPMC8197197 | BioStudies
| S-EPMC7900441 | BioStudies
| S-EPMC4788093 | BioStudies
| E-GEOD-71774 | BioStudies
| E-MTAB-7685 | BioStudies
| S-EPMC8753313 | BioStudies