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Homeotic genes encode DNA-binding transcription factors that specify the identity of a segment or segments in particular body regions of Drosophila. The developmental specificity of these proteins results from their differential regulation of various target genes. This specificity could be achieved by use of different regulatory elements by the homeoproteins or by use of the same elements in different ways. The Ultrabithorax (UBX), abdominal-A (ABD-A), and Antennapedia (ANTP) homeoproteins differentially regulate the Antennapedia P1 promoter in a cell culture cotransfection assay: UBX and ABD-A repress, whereas ANTP activates P1. Either of two regions of P1 can confer this pattern of differential regulation. One of the regions lies downstream and contains homeoprotein-binding sites flanking a 37-bp region called BetBS. ANTP protein activates transcription through the binding sites, whereas UBX and ABD-A both activate transcription through BetBS and use the flanking binding sites to prevent this effect. Thus, homeoproteins can use the same regulatory element but in very different ways. Chimeric UBX-ANTP proteins and UBX deletion derivatives demonstrate that functional specificity in P1 regulation is dictated mainly by sequences outside the homeodomain, with important determinants in the N-terminal region of the proteins.

A differential response element for the homeotics at the Antennapedia P1 promoter of Drosophila.