PROMOTER AND REGULATORY FACTORS OF THE ARRESTIN GENE

抑制蛋白基因的启动子和调控因素

• 批准号: 2608658
• 负责人: TOSHIMICHI SHINOHARA
• 金额: $ 28.15万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2608658
• 关键词: DNA binding protein; DNA footprinting; animal tissue; arrestins; autoradiography; cell differentiation; fusion gene; gel mobility shift assay; gene expression; gene interaction; genetic promoter element; genetic regulatory element; genetically modified animals; hormones; laboratory mouse; methylation; molecular cloning; protein structure function; proteins; recombinant DNA; transcription factor; visual photoreceptor

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.

视网膜感受器杆细胞高度专业 光转导和它们一生都表达了几种主要蛋白质。 虽然，感光细胞限制基因表达的机制 不太了解，它是由 特定的启动子元素和特定的调节核因素。我们 一直在研究抑制蛋白，这是感光棒中的主要蛋白 细胞，在过去的几年中，试图找到一般启动子 光感受器受限表达的元素和调节因素。 我们已经确定了各种物种中的抑制蛋白基因序列，发现 新元素；光感受器保守元件（PCE1）共识。这 PCE1共识是在各种重要的调节区域中发现的 感光细胞特异性基因，它似乎在 确定受感受器受限的基因表达。进一步 定义视网膜感受器特异性基因中的启动子元件， 我们将搜索光感受器特异性启动子中的PCE1共识 计算机库中的序列，如果找到它，我们将定义一个网站 组织特异性所表现出的位置。这些研究将确定 PCE1完全共识。接下来，我们将寻找一个一般的监管因素 调节各种感光特异性基因。我相信这是 由于PCE1共识，我们很可能会找到此类因素 在这些基因中发现了一个一般元素。以前我们有 报告了此类候选因素（BP1，BP2和BP3） 视网膜细胞专门与各种的PCE1位点结合 受感受器特异性启动子。我们将隔离这些因素 使用重组DNA技术并研究 抑制蛋白启动子的每个纯化因子和PCE1 DNA片段。 然后，我们将测试该因素是否也与之相互作用并调节 其他受感受器受限制的启动子。如果我们成功，我们可能 找到一般的感光特定因素。因此，我相信 保守的一般监管元素和核因素的作用 在光感受器特异性基因的表达中的重要作用。在 未来，我们希望隔离调节基因表达的因素 一般监管因素。因此，我们的研究不仅会发现 在正常感光细胞中抑制蛋白的表达，但也是 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。

项目成果

Lens epithelium-derived growth factor promotes photoreceptor survival in light-damaged and RCS rats.

• 发表时间: 2001-04
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: Shigeki Machida;Prem Chaudhry;Toshimichi Shinohara;Dhirendra P. Singh;Venkat N. Reddy;Leo T. Chylack;P. Sieving;R. Bush

Lens epithelium-derived growth factor (LEDGF/p75) and p52 are derived from a single gene by alternative splicing.

晶状体上皮源性生长因子 (LEDGF/p75) 和 p52 通过选择性剪接源自单个基因。

• DOI: 10.1016/s0378-1119(99)00506-5
• 发表时间: 2000
• 期刊: Gene
• 影响因子: 3.5
• 作者: Singh,DP;Kimura,A;ChylackJr,LT;Shinohara,T
• 通讯作者: Shinohara,T

LEDGF: survival of embryonic chick retinal photoreceptor cells.

LEDGF：胚胎鸡视网膜感光细胞的存活率。

• 发表时间: 2000
• 期刊: Investigative ophthalmology & visual science.
• 作者: Nakamura,M;Singh,DP;Kubo,E;ChylackJr,LT;Shinohara,T
• 通讯作者: Shinohara,T

Arrestin and phosducin are expressed in a small number of brain cells.

Arrestin 和 phosducin 在少数脑细胞中表达。

• DOI: 10.1016/s0169-328x(97)00247-7
• 发表时间: 1997
• 期刊: Brain research. Molecular brain research
• 作者: Sunayashiki-Kusuzaki,K;Kikuchi,T;Wawrousek,EF;Shinohara,T
• 通讯作者: Shinohara,T

Oral administration of lens homogenate suppresses antibody production in mice injected with beta-crystallin emulsified in CFA.

口服晶状体匀浆可抑制注射 CFA 乳化 β-晶状体蛋白的小鼠体内抗体的产生。

• DOI: 10.1006/exer.1996.0218
• 发表时间: 1997
• 期刊: Experimental eye research
• 影响因子: 3.4
• 作者: Sueno,T;Inoue,E;Singh,DP;Awata,T;ChylackJr,LT;Shinohara,T
• 通讯作者: Shinohara,T