DIFFERENTIAL STIMULATION BY CCAAT ENHANCER-BINDING PROTEIN ALPHA-ISOFORM OF THE ESTROGEN-ACTIVATED PROMOTER OF THE VERY-LOW-DENSITY APOLIPOPROTEIN-II GENE/

The transcription factors CCAAT/enhancer-binding proteins alpha and be ta (C/EBP alpha and C/EBP beta) are highly expressed in liver and are believed to function in maintaining the differentiated state of the he patocytes, C/EBP alpha appears to be a critical regulator of genes inv olved in metabolic processes. We are interested in the roles of C/EBP in the expression of the very-low-density apolipoprotein II (apoVLDL I I) gene. This gene encodes an avian yolk protein, is induced by estrog ens and is only expressed in liver. To examine the role of C/EBP in ap oVLDL II expression, footprinting and electromobility-shift analysis w ere performed. For three of the protein-binding sites in the apoVLDL I I promoter region, C/EBP alpha and C/EBP beta were identified as the m ajor DNA-binding activities. For one of the C/EBP genes, C/EBP alpha, the effect of the gene products on apoVLDL II transcription was examin ed. From transfection experiments we conclude that maximal estrogen-de pendent activity of the apoVLDL II promoter requires the dual action o f the estrogen receptor and C/EBP. The level of activity is different depending on the nature of the C/EBP alpha translational isoform trans fected, 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 isof orm ratio in the modulation of expression of C/EBP target genes, such as those involved in metabolic processes.