Divergent homeo box proteins recognize similar DNA sequences in Drosophila

A member of a small group of genes in Drosophila that define the segmentation pattern of the early embryo^1-5 even-skipped (eve), which plays a key role in a network of interactions among segmentation genes. It appears to control morphogenesis by regulating the expression of the segmentation gene engrailed (en)^3,4, and by autoregulating its own expression (M. Frasch and M.L., in preparation). Here we show that these regulatory interactions could occur at the level of transcription as a full-length eve protein binds with high affinity to specific sequences located near the 5' ends of the eve and en genes. The en binding sites contain at least one copy of a 10-base pair consensus sequence: T-C-A-A-T-T-A-A-A-T. In contrast, the 5' eve binding sites are relatively G-C rich and do not share obvious similarities with the 10-base pair consensus sequence associated with en. Other homeo box proteins can recognize both classes of eve binding sites, lending support to the proposal that regulatory interactions among homeo box genes involve a competition of different homeo box proteins for similar cis regulatory sequences^6,7.