PROMOTER AND REGULATORY FACTORS OF THE ARRESTIN GENE

视网膜感光杆细胞高度特化， 它们在整个生命过程中表达几种主要蛋白质。 尽管感光细胞的机制限制了基因的表达， 它是由两个人之间的相互作用引发的， 特异性启动子元件和特异性调节核因子。我们 我一直在研究感光杆中的主要蛋白质arrestin 细胞，在过去的几年里，试图找到通用启动子 光感受器限制性表达的元件和调节因子。 我们已经确定了不同物种的arrestin基因序列，并发现了一个 新元件：感光细胞保守元件（PCE1）共识。这 PCE1共识被发现在各种重要的调控区域， 感光细胞特异性基因，它似乎在调节 确定光感受器限制性基因表达。进一步 在视网膜感光细胞特异性基因中定义该启动子元件， 我们将在感光细胞特异性启动子中寻找PCE 1的共有序列 如果我们找到它，我们将确定一个网站， 组织特异性的表现。这些研究将建立 PCE1完全一致。接下来我们将寻找一个通用的调节因子 它调节各种感光细胞特异性基因。我相信这是 我们很可能会发现这样的因素，因为PCE 1的共识， 在这些基因中发现了一个通用元素。以前我们有 报道了这样的候选因子（Bp1，Bp2和Bp3），它们表达于 视网膜细胞排他地结合到各种 感光细胞特异性启动子。我们将分离出这些因素中的每一个 使用重组DNA技术，研究 每个纯化的因子和抑制蛋白启动子的PCE 1 DNA片段。 然后，我们将测试这个因素是否也相互作用和调节 其他感光细胞限制性启动子。如果我们成功了， 寻找一般感光细胞的特异性因子。因此，我认为， 保守的一般调控元件和核因子发挥作用， 在感光细胞特异性基因的表达中起重要作用。在 在未来，我们希望分离出调节基因表达的因子， 一般的调节因素。因此，我们的研究不仅将揭示 arrestin在正常感光细胞中的表达， 对于确定病因和病理变化以及 开发用于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.