PROMOTER AND REGULATORY FACTORS OF THE ARRESTIN GENE

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The retinal photoreceptor rod cells are highly specialized for phototransduction and they express several major proteins throughout life. Although, the mechanism of photoreceptor cell restricted gene expression is not well understood, it is initiated by the interaction between specific promoter elements and specific regulatory nuclear factors. We have been studying arrestin, a principal protein in the photoreceptor rod cells, in the last several years and trying to find general promoter elements and regulatory factors for photoreceptor restricted expression. We have determined arrestin gene sequences in various species and found a novel element; the photoreceptor conserved element (PCE1) consensus. This PCE1 consensus is found in the important regulatory region of various photoreceptor specific genes and it appears to play a regulatory role in determining the photoreceptor restricted gene expression. To further define this promoter element in the retinal photoreceptor specific genes, we will search for the PCE1 consensus in photoreceptor specific promoter sequences in the computer banks and if we find it, we will define a site where the tissue specificity exhibits. These studies will establish the PCE1 consensus fully. Next we will search for a general regulatory factor which regulates the various photoreceptor specific genes. I believe it is highly probable that we will find such factors since the PCE1 consensus, a general element, has been found in these genes. Previously we have reported such candidate factors (Bp1, Bp2, and Bp3) which express in retinal cells exclusively and bind to the PCE1 site of the various photoreceptor specific promoters. We will isolate each of these factors using recombinant DNA techniques and study the exact interaction between each purified factor and the PCE1 DNA fragment of the arrestin promoter. Then, we will test whether this factor also interacts with and regulates the other photoreceptor restricted promoters. If we are successful, we may find general photoreceptor specific factors. Thus, I believe that highly conserved general regulatory elements and nuclear factors play an important role in the expression of the photoreceptor specific genes. In the future, we hope to isolate factors which regulate gene expression of the general regulatory factors. Thus, our studies will not only uncover the expression of arrestin in normal photoreceptor cells but are also important for determining the etiology and pathological changes as well as developing diagnostic tools for retinal degeneration in human.