Genome-wide Coactivation Analysis of PGC-1alpha Identifies BAF60a As a Regulator of Hepatic Lipid Metabolism

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2008 Aug 6

PMID 18680712

Citations 112

Authors

Siming Li

Chang Liu

Na Li

Tong Hao

Ting Han

David E Hill

Marc Vidal

Jiandie D Lin

Affiliations

Soon will be listed here.

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 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.

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