COLLAGEN GENE REGULATION IN DEVELOPMENT AND DISEASE

发育和疾病中的胶原蛋白基因调控

• 批准号: 6374958
• 负责人: MICHAEL BREINDL
• 金额: $ 23.78万
• 依托单位: SAN DIEGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-25 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6374958
• 关键词: bone marrow; cell differentiation; chemical structure function; chromatin; collagen; connective tissue development; developmental genetics; fibrosis; gene expression; genetic regulation; genetic regulatory element; genetically modified animals; green fluorescent proteins; introns; laboratory mouse; nucleic acid sequence; nucleic acid structure; protein structure function; reporter genes; tissue /cell culture; transfection

DESCRIPTION: (Adapted from the applicant's abstract) - Type I collagen, the most abundant protein in vertebrates, has diverse biologic function, including providing tensile strength to connective tissues, forming the framework of connective tissue in all major internal organs, and promoting cell migration and differentiation during development. Thus, a detailed (but still lacking) knowledge of the regulation of expression of the genes encoding type I collagen is essential for understanding these various processes and the diseases that can affect them. The applicant has a long and successful track record in analyzing the 5' flanking sequence of the a1(I) collagen gene. As the applicant points out, numerous studies have tried to address the cell-specific regulation of expression of the type I collagen genes yet these mechanisms are still not understood. In particular the role of distal elements in the a1(I) collagen gene and of the chromatin structure is unknown. Thus, the long-term goal of this proposal is to understand at the molecular level, the complex mechanisms involved in the stage and tissue-specific regulation of the a1(I) collagen gene. The applicant proposes to achieve this goal of analyzing the role of chromatin structure and the nuclear matrix in a1(I) collagen regulation of expression. The five specific aims are: To identify regulatory elements that account for the high level of a1(I) collagen in cells that produce large amounts of type I collagen; to identify and analyze regulatory elements involved in the chromatin loop organization of the a1(I) collagen domain; to analyze the functions of distal regulatory elements in transgenic mice; to analyze a1(I) regulatory elements in normal development and differentiation and in fibrotic disorders.

描述：（改编自申请人的摘要） - I型胶原蛋白， 脊椎动物中最丰富的蛋白质具有多种生物功能， 包括为结缔组织提供拉伸强度，形成 在所有主要内部器官中结缔组织的框架，并促进 细胞迁移和开发过程中的分化。 因此，详细 （但仍然缺乏）对基因表达的调节的了解 编码I型胶原蛋白对于理解这些各种胶原蛋白至关重要 过程和可能影响它们的疾病。 申请人有很长的 并成功地分析了5'侧翼序列 A1（i）胶原蛋白基因。 正如申请人指出的那样，许多研究 试图解决I型表达的细胞特异性调节 胶原蛋白基因仍然尚不清楚这些机制。 尤其 远端元素在A1（I）胶原基因和染色质中的作用 结构未知。 因此，该提议的长期目标是 在分子水平上理解，涉及的复杂机制 A1（I）胶原基因的阶段和组织特异性调节。 这 申请人建议实现分析染色质作用的目标 A1（i）表达胶原蛋白调节中的结构和核基质。 五个具体目的是：确定说明的监管要素 对于高水平的A1（i）胶原蛋白，产生大量的胶原蛋白 I型胶原蛋白；识别和分析与 A1（i）胶原蛋白结构域的染色质循环组织；分析 转基因小鼠远端调节元件的功能；分析A1（i） 正常发展和分化的监管因素以及 纤维化疾病。