Functional dissection of Drosophila TFIID

果蝇 TFIID 的功能解剖

• 批准号: 7096538
• 负责人: FRANK U SAUER
• 金额: $ 29.3万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7096538
• 关键词: DNA directed RNA polymerase; Drosophilidae; RNA interference; biotechnology; cell cycle; chromatin immunoprecipitation; eukaryote; functional /structural genomics; gene expression; gene expression profiling; gene induction /repression; genetic transcription; in situ hybridization; laboratory rabbit; microarray technology; molecular shape; polymerase chain reaction; transcription factor; DNA directed RNA polymerase; Drosophilidae; RNA interference; biotechnology; cell cycle; chromatin immunoprecipitation; eukaryote; functional /structural genomics; gene expression; gene expression profiling; gene induction /repression; genetic transcription; in situ hybridization; laboratory rabbit; microarray technology; molecular shape; polymerase chain reaction; transcription factor

DESCRIPTION (provided by applicant): Activation of eukaryotic transcription depends on a refined interplay of regulatory proteins with their target genes. Our long-term goal is to elucidate the mechanisms underlying regulation of metazoan gene expression as a prerequisite for the development of diagnostic and therapeutic assays that detect and attenuate human diseases. The specific hypothesis behind the proposed research is that the "TBP-associated factors" (TAFs) in the general transcription factor TFIID play an important role in metazoan transcription. That hypothesis is based on the observations that 1) mutations in TAFs are recessive lethal, 2.) TAFs interact with activators, 3.) TAFs mediate binding of TFIID to promoters, 4.) TAFs mediate the postsynthetic modification of histones and GTFs, and 5.) TAFs play an important role in various biological processes. Based on these results the main experimental focus of this proposal is on the functional importance of TAFs for transcription activation in the context of a metazoan genome. The specific aims are to: 1. To dissect the functional importance of TAF1 activities in regulation of transcription. TAF1 plays an important role in transcription activation by postsynthetic modification of histones and GTFs, interacting with TBP, mediating the recruitment of TFIID to promoters. We will correlate genome-wide transcription profiling with chromatin immunoprecipitation experiments to elucidate the functional importance of the various activities in TAF1 in metazoan transcription. 2. To dissect the functional importance of TAFs in activation of transcription in Drosophila. The correlation of the transcription status of Drosophila genes with the presence of TAFs, TAF-mediated protein modifications, activators, and the RNA polymerase II transcription machinery (GTM) at promoters will elucidate the functional importance of TAFs in transcription activation. 3. To dissect the role of TAFs in the execution of biological processes in vivo. We will correlate the transcription of specific genes with the presence of TAFs, TAF-mediated protein modifications, and the GTM at the promoters of the genes to elucidate the functional importance of TAFs for body pattern formation, cell cycle progression, and epigemetic activation.

描述（由申请人提供）：真核转录的激活取决于调节蛋白与目标基因的精致相互作用。我们的长期目标是阐明后生基因表达的基础机制，这是开发检测和减弱人类疾病的诊断和治疗测定法的先决条件。拟议的研究背后的特定假设是，一般转录因子TFIID中的“与TBP相关因素”（TAFS）在后生动物转录中起重要作用。该假设是基于观察结果，即1）TAF中的突变是隐性致死的。2。）TAF与激活剂相互作用，3。）TAF介导TFIID与启动子的结合，4。）TAF介导组蛋白和GTF的结合后修饰，以及5.）TAF在各种生物过程中起重要作用。基于这些结果，该提案的主要实验重点是在后生基因组中TAFS在转录激活的功能重要性上。具体目的是： 1。阐述TAF1活性在调节转录中的功能重要性。 TAF1通过组蛋白和GTF的合并后修饰在转录激活中起重要作用，与TBP相互作用，介导TFIID募集到启动子为启动子。我们将将全基因组的转录分析与染色质免疫沉淀实验相关联，以阐明Metazoan转录中TAF1中各种活动的功能重要性。 2。阐述TAF在果蝇中转录激活中的功能重要性。果蝇基因的转录状态与TAF，TAF介导的蛋白质修饰，激活剂和RNA聚合酶II转录机制（GTM）的存在相关性将阐明TAF在转录激活中的功能重要性。 3。剖析TAF在体内生物过程中的作用中的作用。我们将将特定基因的转录与TAFS的存在，TAF介导的蛋白质修饰以及在基因启动子处的GTM相关联，以阐明TAFS在身体模式形成，细胞周期进展和经远程远期激活方面的功能重要性。