The G0/G1 switch gene 2 is a novel PPAR target gene

PPARs (peroxisome-proliferator-activated receptors) alpha, beta/delta and gamma are a group of transcription factors that are involved in numerous processes. including lipid metabolism and adipogenesis. By comparing liver mRNAs of wild-type and PPAR alpha-null mice using microarrays, a novel putative target gene of PPAR alpha, G0S2 (G(0)/G(1) switch gene 2), was identified. Hepatic expression of G0S(2) was up-regulated by fasting and by the PPAR alpha agonist Wy14643 in a PPAR alpha-depenclent manner. Surprisingly, the G0S(2) mRNA level was highest in brown and white adipose tissue and was greatly up-regulated during mouse 3T3-L1 and human SGBS (Simpson-Golabi-Behniel syndrome) adipogenesis. Transactivation, gel shift and chromatin immunoprecipitation assays indicated that G0S2 is a direct PPAR gamma and probable PPAR alpha target gene with a functional PPRE (PPAR-responsive element) in its promoter. Up-regulation of G0S2 mRNA seemed to be specific for adipogenesis, and was not observed during osteogenesis or myogenesis. In 3T3-L1 fibroblasts, expression of G0S2 was associated with growth arrest, which is required for 3T3-L1 adipogenesis. Together, these data indicate that G0S2 is it novel target gene of PPARs that may be involved ill adipocyte differentiation.