Sequential repression and activation of the CCAAT enhancer-binding protein-alpha (C/EBPalpha ) gene during adipogenesis.
CCAAT enhancer-binding protein-alpha (C/EBPalpha) functions as a pleiotropic transcriptional activator of adipocyte genes during adipogenesis. Nuclear factor C/EBP undifferentiated protein (CUP), an isoform of activator protein-2alpha (AP-2alpha), binds to repressive elements in the C/EBPalpha gene promoter, silencing the gene until late in the differentiation program. The CUP regulatory element overlaps a Sp (GT-box) element in the promoter to which Sp3 (or Sp1) can bind. Binding by Sp3 or Sp1 and CUP/AP2-alpha is mutually exclusive. Sp3 is a strong transcriptional activator of the C/EBPalpha gene promoter in 3T3-L1 preadipocytes and Schneider cells, this activation being repressed by CUP/AP-2alpha. Sp3 is expressed throughout differentiation, whereas CUP/AP-2alpha, which is expressed only by preadipocytes, is down-regulated during differentiation coincident with transcription of the C/EBPalpha gene. Thus, CUP/AP-2alpha delays access of Sp3 to the Sp regulatory element, preventing premature expression of C/EBPalpha and thereby interference by C/EBPalpha (which is antimitotic) with mitotic clonal expansion, an essential early event in the differentiation program.
Jiang
M S
MS
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Lane
M D
MD
D016475:3T3 Cells; D017667:Adipocytes; D000818:Animals; D001665:Binding Sites; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics*; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005786:Gene Expression Regulation; D005807:Genes, Overlapping; D006801:Humans; D007700:Kinetics; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009841:Oligonucleotides; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D051705:Sp3 Transcription Factor; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D022763:CCAAT-Enhancer-Binding Protein-alpha; C082509:CUP protein, human; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D009841:Oligonucleotides; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; C497122:Sp3 protein, mouse; C493673:TFAP2A protein, human; C493674:TfAP-2 protein, Drosophila; C493668:Tfap2a protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D051705:Sp3 Transcription Factor