TELOKIN GENE REGULATION IN SMOOTH MUSCLE

描述(改编自《调查者摘要》)：改变的收缩 蛋白表达和平滑肌细胞增殖增加 许多血管和肺部疾病的特点。长期目标 这项提议的目的是解开调控基因表达的机制 一种结合小肌球蛋白的平滑肌特异表达的端粒蛋白 蛋白质，将被阐明。需要评估的总体假设是 组织特异性核蛋白与脑内顺式作用元件的结合 端粒蛋白启动子，调节平滑肌组织中的端粒蛋白转录。一个 这一假说的推论是，telokin的差异表达 在内脏和血管平滑肌中，结果来自不同的水平 或在每一个核蛋白中形成独特的核蛋白 平滑的肌肉组织。为解决这一问题，提出了四个具体目标 假设。实验将首先确定telokin表达是否 限制在整个发育过程中的平滑肌细胞，并决定 端粒酶蛋白相对其他平滑蛋白表达的时间模式 肌肉特有的蛋白质。端粒酶启动子中的顺式作用元件 将确定在平滑肌组织中调节端粒蛋白表达的分子 在培养的细胞和转基因小鼠中。与以下因素相关的因素 然后将确定和克隆重要的监管要素。一次 调控因子已被克隆，它们的组织和发育模式 将对其进行分析，并对其在表达调控中的作用进行分析 已经确定了端粒蛋白和其他平滑肌肉基因。这些研究将 帮助解开复杂的互动网络，最终导致 平滑肌肉分化，并提供可用于 设计平滑肌特异性基因传递系统。

DESCRIPTION (Adapted from Investigator's Abstract): Altered contractile protein expression and increased smooth muscle cell proliferation are characteristics of many vascular and pulmonary diseases. The long-term goal of this proposal is to unravel the mechanisms regulating the expression of smooth muscle-specific expression of telokin, a small myosin binding protein, will be elucidated. The overall hypothesis to be evaluated is that binding of tissue-specific nuclear proteins to cis-acting elements in the telokin promoter, regulates telokin transcription in smooth muscle. A corollary of this hypothesis is that the differential expression of telokin in visceral and vascular smooth muscle, results from either different levels of nuclear regulatory proteins or form unique nuclear proteins in each of the smooth muscle tissues. Four Specific Aims are proposed to address this hypothesis. Experiments will first determine if telokin expression is restricted to smooth muscle cells throughout development, and determine the temporal pattern of telokin expression relative to other smooth muscle-specific proteins. The cis-acting elements in the telokin promoter that regulate telokin expression in smooth muscle tissues will be identified in cultured cells and in transgenic mice. The factors that bind to important regulatory elements will then be identified and cloned. Once regulatory factors have been cloned, their tissue and developmental pattern of expression will be analyzed and their role in regulating the expression of telokin and other smooth muscle genes determined. These studies will help unravel the complex network of interactions that ultimately results in smooth muscle differentiation and provide reagents that can be used to design smooth muscle-specific gene delivery systems.