Erx, a novel retina-specific homeodomain transcription factor, can interact with Ret 1/PCEI sites

Our previous studies on the transcriptional regulation of rod opsin gene expression had defined a strikingly conserved element, Ret 1/PCEI, present in the upstream regulatory regions of opsin and other photoreceptor-specific genes. This element interacts with a 40 kDa, developmentally regulated, retina-specific protein. In this study we report the cloning of the novel retina-specific homeodomain protein Erx. Erx contains a homeodomain that is 79% homologous to that of Drosophila empty spiracles. This 40 kDa protein can interact with the Ret 1 element in electrophoretic mobility shift assays. Mutation of key residues in Ret 1 eliminates all Erx binding. Transient transfection of Y79 retinobalstoma cells with Erx leads to significant transcriptional activation of a reporter gene via Ret 1 elements. We conclude that Erx is the Ret 1 binding activity. This is the first example of a Q50 homeodomain protein expressed in retinal photoreceptors.