Differential stimulation by CCAAT/enhancer-binding protein alpha isoforms of the estrogen-activated promoter of the very-low-density apolipoprotein II gene.
The transcription factors CCAAT/enhancer-binding proteins alpha and beta (C/EBP alpha and C/EBP beta) are highly expressed in liver and are believed to function in maintaining the differentiated state of the hepatocytes. C/EBP alpha appears to be a critical regulator of genes involved in metabolic processes. We are interested in the roles of C/EBP in the expression of the very-low-density apolipoprotein II (apoVLDL II) gene. This gene encodes an avian yolk protein, is induced by estrogens and is only expressed in liver. To examine the role of C/EBP in apoVLDL II expression, footprinting and electromobility-shift analysis were performed. For three of the protein-binding sites in the apoVLDL II promoter region, C/EBP alpha and C/EBP beta were identified as the major DNA-binding activities. For one of the C/EBP genes, C/EBP alpha, the effect of the gene products on apoVLDL II transcription was examined. From transfection experiments we conclude that maximal estrogen-dependent activity of the apoVLDL II promoter requires the dual action of the estrogen receptor and C/EBP. The level of activity is different depending on the nature of the C/EBP alpha translational isoform transfected, the full-length C/EBP alpha polypeptide being the most active isoform and the N-terminally truncated isoform being moderately active. The present results suggest a role of C/EBP alpha translational isoform ratio in the modulation of expression of C/EBP target genes, such as those involved in metabolic processes.
Calkhoven
C F
CF
Laboratory of Biochemistry, University of Groningen, The Netherlands.
Snippe
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D000818:Animals; D001053:Apolipoproteins / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D002645:Chickens; D015342:DNA Probes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D045166:Estradiol Congeners / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008079:Lipoproteins, VLDL / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D001053:Apolipoproteins; D022762:CCAAT-Enhancer-Binding Proteins; D015342:DNA Probes; D004268:DNA-Binding Proteins; D045166:Estradiol Congeners; D004967:Estrogens; D008079:Lipoproteins, VLDL; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D014157:Transcription Factors; C027610:apolipoprotein VLDL II; D004997:Ethinyl Estradiol; C011310:moxestrol