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 PPARalpha-null mice using microarrays, a novel putative target gene of PPARalpha, G0S2 (G0/G1 switch gene 2), was identified. Hepatic expression of G0S2 was up-regulated by fasting and by the PPARalpha agonist Wy14643 in a PPARalpha-dependent manner. Surprisingly, the G0S2 mRNA level was highest in brown and white adipose tissue and was greatly up-regulated during mouse 3T3-L1 and human SGBS (Simpson-Golabi-Behmel syndrome) adipogenesis. Transactivation, gel shift and chromatin immunoprecipitation assays indicated that G0S2 is a direct PPARgamma and probable PPARalpha 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 a novel target gene of PPARs that may be involved in adipocyte differentiation.
Zandbergen
Fokko
F
Nutrition, Metabolism and Genomics Group, Wageningen University, 6700 EV, Wageningen, The Netherlands.
Mandard
Stéphane
S
Escher
Pascal
P
Tan
Nguan Soon
NS
Patsouris
David
D
Jatkoe
Tim
T
Rojas-Caro
Sandra
S
Madore
Steve
S
Wahli
Walter
W
Tafuri
Sherrie
S
Müller
Michael
M
Kersten
Sander
S
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017353:Gene Deletion; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020218:Response Elements / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity; D015854:Up-Regulation
D018797:Cell Cycle Proteins; C508073:G0S2 protein, human; C508072:G0S2 protein, mouse; D047493:PPAR alpha; D012333:RNA, Messenger