PROMOTER AND REGULATORY FACTORS OF THE ARRESTIN GENE

视网膜光感受器视杆细胞高度专门化 光传导，它们在整个生命过程中表达几种主要的蛋白质。 虽然，光感受器细胞限制基因表达的机制 没有被很好地理解，它是由 特定的启动子元件和特定的调控核因子。我们 一直在研究arrestin，这是光感受器棒中的主要蛋白质 细胞，在过去的几年里，试图寻找普遍的启动子 光感受器限制性表达的元件和调控因子。 我们已经测定了不同物种的arrestin基因序列，并发现了一种 新元件；光感受器保守元件(PCE1)共识。这 在各种不同的重要监管区域发现了PCE1共识 光感受器特异性基因，它似乎在 光感受器限制性基因表达的测定。为了进一步 在视网膜光感受器特定基因中定义这个启动子元件， 我们将在光感受器特异性启动子中寻找PCE1共识 如果我们找到了它，我们就会定义一个地点 组织特异性表现出来的地方。这些研究将确立 PCE1完全达成共识。接下来，我们将寻找一个一般性的监管因素 它调节各种光感受器特异基因。我想是的 自PCE1共识以来，我们极有可能找到这样的因素， 在这些基因中发现了一种普遍的元素。以前我们有过 已报道的候选因子(BP1、BP2和BP3)在 视网膜细胞专一地结合到PCE1部位的各种 光感受器特异性启动子。我们将分离这些因素中的每一个 利用重组DNA技术并研究它们之间的确切相互作用 每个纯化因子和arrestin启动子的PCE1DNA片段。 然后，我们将检验这个因素是否也相互作用和调节 另一种光感受器限制启动子。如果我们成功了，我们可能会 找出一般的感光细胞特异性因子。因此，我高度相信， 保守的一般监管要素和核因素发挥着作用 在光感受器特异基因的表达中起重要作用。在……里面 在未来，我们希望分离出调控基因表达的因子 一般监管因素。因此，我们的研究不仅将揭示 Arrestin在正常光感受器细胞中的表达 对于确定病因和病理变化以及 开发人类视网膜变性的诊断工具。

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.