| First Author | Li S | Year | 2008 |
| Journal | Cell Metab | Volume | 8 |
| Issue | 2 | Pages | 105-17 |
| PubMed ID | 18680712 | Mgi Jnum | J:140133 |
| Mgi Id | MGI:3811973 | Doi | 10.1016/j.cmet.2008.06.013 |
| Citation | Li S, et al. (2008) Genome-wide coactivation analysis of PGC-1alpha identifies BAF60a as a regulator of hepatic lipid metabolism. Cell Metab 8(2):105-17 |
| abstractText | 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 central components of the regulatory network that controls mitochondrial function in mammalian cells. Here we describe a genome-wide coactivation assay to globally identify transcription factors and cofactors in this pathway. These analyses revealed a molecular signature of the PGC-1alpha transcriptional network and identified BAF60a (SMARCD1) as a molecular link between the SWI/SNF chromatin-remodeling complexes and hepatic lipid metabolism. Adenoviral-mediated expression of BAF60a stimulates fatty acid beta-oxidation in cultured hepatocytes and ameliorates hepatic steatosis in vivo. PGC-1alpha mediates the recruitment of BAF60a to PPARalpha-binding sites, leading to transcriptional activation of peroxisomal and mitochondrial fat-oxidation genes. These results define a role for the SWI/SNF complexes in the regulation of lipid homeostasis. |
