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.
Falb
D
D
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Maniatis
T
T
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D005075:Biological Evolution; D022762:CCAAT-Enhancer-Binding Proteins; D004247:DNA / Q000235:genetics; D016172:DNA Fingerprinting; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000201:enzymology*; D004742:Enhancer Elements, Genetic; D005216:Fat Body / Q000201:enzymology; D005260:Female; D015870:Gene Expression; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
C073554:Aef1 protein, Drosophila; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D004247:DNA; D000426:Alcohol Dehydrogenase