Abstract
DAX-1 is an atypical nuclear receptor (NR) which functions primarily as a transcriptional corepressor of other NRs via heterodimerization. Peroxisome proliferator-activated receptor (PPAR) gamma is a ligand-dependent NR which performs a key function in adipogenesis. In this study, we evaluated a novel cross-talk mechanism between DAX-1 and PPARgamma. Transient transfection assays demonstrated that DAX-1 inhibits the transactivity of PPARgamma in a dose-dependent manner. DAX-1 directly competed with the PPARgamma coactivator (PGC)-1alpha for binding to PPARgamma. Endogenous levels of DAX-1 were significantly lower in differentiated 3T3-L1 adipocytes as compared to preadipocytes. Using a retroviral expression system, we demonstrated that DAX-1 overexpression downregulates the expression of PPARgamma target genes, resulting in an attenuation of adipogenesis in 3T3-L1 cells. Our results suggest that DAX-1 acts as a corepressor of PPARgamma and performs a potential function in the regulation of PPARgamma-mediated cellular differentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Adipogenesis / genetics*
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Animals
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Binding, Competitive
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Cell Line
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DAX-1 Orphan Nuclear Receptor
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation*
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Heat-Shock Proteins / antagonists & inhibitors
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Heat-Shock Proteins / metabolism
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Humans
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Mice
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PPAR gamma / antagonists & inhibitors*
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PPAR gamma / metabolism
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / metabolism
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Transcription, Genetic
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Transcriptional Activation
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Transfection
Substances
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DAX-1 Orphan Nuclear Receptor
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DNA-Binding Proteins
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Heat-Shock Proteins
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NR0B1 protein, human
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Nr0b1 protein, mouse
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PPAR gamma
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PPARGC1A protein, human
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Receptors, Retinoic Acid
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Repressor Proteins
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Transcription Factors