Krox20 stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms.
Krox20 is a zinc finger-containing transcription factor that is abundantly expressed in adipose tissue. However, its role in fat cell differentiation has not been established. In cultured 3T3-L1 cells, Krox20 is rapidly induced by serum stimulation. Overexpression of Krox20 in both 3T3-L1 preadipocytes and multipotent NIH3T3 cells promotes adipogenesis in a hormone-dependent manner. Conversely, RNAi-mediated loss of Krox20 function reduced adipogenesis in 3T3-L1 cells. Ectopic expression of Krox20 can transactivate the C/EBPbeta promoter and increase C/EBPbeta gene expression in 3T3-L1 preadipocytes. RNAi-mediated knockdown of C/EPBbeta diminished Krox20's proadipogenic effect. Finally, coexpression of Krox20 and C/EBPbeta in naive NIH3T3 cells resulted in the pronounced induction of a fully differentiated adipocyte phenotype, an effect previously observed only with PPARgamma. These data indicate that Krox20 is necessary for adipogenesis and that, when overexpressed, Krox20 potently stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms.
Chen
Zhu
Z
Laboratory of Molecular Genetics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Torrens
Javier I
JI
Anand
Ashim
A
Spiegelman
Bruce M
BM
Friedman
Jeffrey M
JM
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D051767:Early Growth Response Protein 2; D020868:Gene Silencing; D017930:Genes, Reporter; D006728:Hormones / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D047495:PPAR gamma / Q000378:metabolism; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D016335:Zinc Fingers
D022782:CCAAT-Enhancer-Binding Protein-beta; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D006728:Hormones; D047495:PPAR gamma; D034741:RNA, Small Interfering; D014157:Transcription Factors; D008156:Luciferases