DETERMINANTS OF GENE REGULATION

基因调控的决定因素

• 批准号: 2177313
• 负责人: DOUGLAS R. CAVENER
• 金额: $ 18.96万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2177313
• 关键词: Drosophilidae; RNase protection assay; biochemical evolution; cytogenetics; developmental genetics; enzyme activity; gene expression; genetic library; genetic manipulation; genetic promoter element; genetic regulatory element; genetic transcription; glucose dehydrogenases; linkage mapping; molecular cloning; nucleic acid hybridization; nucleic acid probes; nucleic acid sequence; regulatory gene; sex determination; species difference; transcription factor

The longterm goal of the proposed research is to determine how genetic regulatory systems are determined by the joint contribution of their developmental and evolutionary histories. The Drosophila glucose dehydrogenase gene (Gld) will be used as a model system to study these determinants of gene regulation because Gld's tissue-specific regulation in the adult reproductive tract is highly variable among a variety of species in the genus Drosophila. The research strategy will be to use a combination of in vitro mutagenesis and gene transformation to critically test hypotheses regarding the role of cis-elements and trans-acting factors responsible for species' differences in developmental expression of GLD. The specific aims are largely focused on elucidating the regulatory factors underlying GLD expression in the reproductive organs of both males and females, and, in parallel, identifying regulatory differences between species. Since the sex- determination genes tra and tra-2 are required for the unique tissue- specific pattern of GLD expression in D. melanogaster, the Gld regulatory elements that respond to them will be mapped. Misregulation of tra and tra-2 in D. melanogaster leads to ectopic patterns of GLD expression in the reproductive tract that mimic normal patterns seen other Drosophila species. A hypothesis that other species' Gld genes differ in their response to the sex-determination genes will be tested. A newly devised genetic method for identifying genes that encode tissue specific transcription factors will be used to isolate such genes that regulate Gld. Knowledge of gene function alone provides insufficient and sometimes misleading information for understanding why genes are expressed in certain tissues. The proposed research should provide a deeper understanding of how evolution and development affect gene regulation thereby increasing our understanding of how perturbations in genetic regulatory systems can result in human genetic diseases.

拟议研究的长期目标是确定遗传 监管系统取决于其共同贡献 发展和进化史。果蝇葡萄糖 脱氢酶基因（GLD）将用作研究这些模型系统 基因调节的决定因素，因为GLD的组织特异性 成人生殖道中的调节在A 果蝇属的种类。研究策略将 使用体外诱变和基因转化的组合 批判性检验有关顺式元素和 造成物种差异的跨作用因素 GLD的发展表达。具体目标主要集中 阐明在GLD表达中的调节因素 男性和女性的生殖器官，并同时 识别物种之间的调节差异。 自性别 - 确定基因Tra和Tra-2是独特的组织所需的 D. melanogaster中GLD表达的特定模式，GLD 对响应它们的监管要素将被映射。正直 D. melanogaster中的Tra和Tra-2导致GLD的异位模式 在生殖道中表达模仿正常模式 其他果蝇。其他物种的GLD基因的假设 它们对性别确定基因的反应不同。 一种新设计的遗传学方法，用于鉴定编码组织的基因 特定的转录因子将用于分离这种基因 调节GLD。 仅对基因功能的知识提供了不足，有时甚至是 误导信息以理解为什么在 某些组织。 拟议的研究应更深入 了解进化和发展如何影响基因调节 从而增加我们对遗传扰动的理解 调节系统可能导致人类遗传疾病。