A conserved regulatory element present in all Drosophila rhodopsin genes mediates Pax6 functions and participates in the fine-tuning of cell-specificexpression

The Drosophila rhodopsin genes (rh s) represent a unique family of highly r egulated cell-specific genes. where each member has its own expression patt ern in the visual system. Extensive analysis of the rhs has revealed severa l functional elements that are involved in cell-specificity. We have invest igated the functional role of the RCSI/P3 site that is found in the proxima l promoter of all Drosophila rh genes. This sequence is remarkably conserve d in evolution and is located 15-30 bp upstream of the TATA box. We have pr eviously shown that, in the context of the rh1 promoter, this element is re cognized in vivo by a Pax6 protein, the master regulator of eye development . Thus, rh regulation might represent the ancestral function of Pax6. Here, we investigated the role of the RCSI/P3 sequence in the other rh genes and show that they also mediate Path function. We also tested the potential im pact of the various RCSI/P3 sequences on the precise cell-specific expressi on of rh genes. Our results demonstrate that, even though all RCSI/P3 seque nces bind Path, they are clearly distinct in various rh promoters and these differences are conserved throughout evolution: RCSI/P3 appears to partici pate in the fine-tuning of cell-specificity. We also show that Pax6 or a re lated Pax protein may be involved in the regulation of olfactory genes. The refore, in addition to performing a global photoreceptor-specific function, RCSI also appears to mediate the combined action of Pax6 and other factors and to contribute to rh regulation in subsets of photoreceptors. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.