RUI: Tissue-Specific Gene Regulation in Drosophila

RUI：果蝇的组织特异性基因调控

• 批准号: 0110238
• 负责人: Craig Woodard
• 金额: $ 35万
• 依托单位: Mount Holyoke College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0110238&HistoricalAwards=false
• 关键词: RUI; Tissue; Specific; Gene; Regulation

Steroid hormones control a wide range of physiological and developmental processes in higher organisms, acting in conjunction with receptor proteins to regulate the stage- and tissue-specific transcription of target genes. The study of steroid receptor genetics and biochemistry has led to enormous advances in our understanding of how steroids activate gene transcription. Remarkably, a single hormone appears to be capable of inducing extremely different responses, depending on cellular and temporal context. Although much is understood about how steroid receptors control transcription in cultured mammalian cells, little is understood about how these effects on gene expression result in the dramatic stage- and tissue-specific developmental changes associated with steroid hormone action. This project makes use of the fruit fly, Drosophila melanogaster, to examine how steroid-induced changes in gene expression control specific cellular responses during development. Pulses of the steroid 20-hydroxyecdysone (ecdysone) trigger genetic regulatory hierarchies that direct both destruction of tissues by programmed cell death, and morphogenesis (the formation of structures). This project focuses on the roles of nuclear receptor beta-FTZ-F1 and the ecdysone receptor in controlling the stage- and tissue-specific expression of a set of ecdysone-inducible "early" genes, including BR-C, E74A, E75A and E93. In this examination of the molecular mechanism underlying these gene regulatory phenomena, particular attention is paid to the regulation of E93. E93 is precisely regulated by ecdysone in dying cells, where it induces a programmed cell death response. In certain tissues, such as the larval salivary gland, the regulation of E93 by ecdysone depends on beta-FTZ-F1, which appears to provide E93 with the competence to respond to the hormone. Goals of this project are to address how members of the nuclear receptor superfamily regulate the stage- and tissue-specific expression of E93, as well as BR-C, E74A, and E75A during development, and to shed light on the mechanisms by which steroid hormones elicit distinct biological responses.

甾体激素控制着高等生物的广泛生理和发育过程，与受体蛋白一起调节靶基因的阶段特异性和组织特异性转录。 类固醇受体的遗传学和生物化学的研究导致了我们对类固醇如何激活基因转录的理解的巨大进步。 值得注意的是，一种激素似乎能够诱导极其不同的反应，这取决于细胞和时间背景。虽然很多了解类固醇受体如何控制在培养的哺乳动物细胞中的转录，很少了解这些对基因表达的影响如何导致与类固醇激素作用相关的戏剧性的阶段和组织特异性发育变化。 该项目利用果蝇（Drosophila melanogaster）来研究类固醇诱导的基因表达变化如何控制发育过程中的特定细胞反应。 类固醇20-羟基蜕皮激素（ecdysone）的脉冲触发遗传调节层级，其通过程序性细胞死亡和形态发生（结构的形成）来指导组织的破坏。 该项目的重点是核受体β-FTZ-F1和蜕皮激素受体在控制一组蜕皮激素诱导的“早期”基因（包括BR-C，E74 A，E75 A和E93）的阶段和组织特异性表达中的作用。 在这些基因调控现象背后的分子机制的检查，特别注意的是E93的调节。E93在垂死细胞中受到蜕皮激素的精确调节，在那里它诱导程序性细胞死亡反应。 在某些组织中，如幼虫唾液腺，蜕皮激素对E93的调节依赖于β-FTZ-F1，β-FTZ-F1似乎为E93提供了响应激素的能力。 该项目的目标是解决核受体超家族成员如何调节E93的阶段和组织特异性表达，以及BR-C，E74 A和E75 A在发育过程中，并阐明类固醇激素引起不同生物反应的机制。