A CONSERVED REGULATORY UNIT IMPLICATED IN TISSUE-SPECIFIC GENE-EXPRESSION IN DROSOPHILA AND MAN

The Drosophila melanogaster alcohol dehydrogenase (Adh) gene is expressed in a specific set of tissues during larval development and in adults. Expression in the adult fat body is controlled by the Adh adult enhancer (AAE). Previous studies identified a negative regulatory element in the AAE and a protein that binds specifically to this sequence [adult enhancer factor-1 (AEF-1)]. Here, we show that the AEF-1-binding site in the AAE and in two other Drosophila fat body enhancers overlaps a sequence recognized by the mammalian transcription factor CCAAT/enhancer-binding protein (C/EBP). Remarkably, these two proteins also bind specifically to overlapping sites in a liver-specific regulatory element of the human Adh gene. Cotransfection experiments in mammalian cells reveal that C/EBP stimulates the activity of the AAE by 50-fold, and this activity can be suppressed by AEF-1. In addition, AEF-1 prevents C/EBP binding in vitro, and displaces prebound C/EBP. Thus, a tissue-specific regulatory unit consisting of one positive and one negative regulatory element has been conserved between Drosophila and man.