Functional dissection of Drosophila TFIID

果蝇 TFIID 的功能解剖

基本信息

批准号：
7469439
负责人：
FRANK U SAUER
金额：
$ 28.45万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-01 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7469439
关键词：
Attenuated Binding Biological Assay Biological Process Body Patterning Bromodomain Cell Cycle Cell Cycle Progression Cell Cycle Regulation Cells Chromatin Complex Computer Simulation Development Diagnostic Dissection Drosophila genome Drosophila genus Epigenetic Process Gene Expression Gene Targeting General Transcription Factors Genes Genetic Genetic Transcription Genome Goals Heterochromatin Histones Homeobox Genes Link Mediating Methylation Modification Molecular Mutation Numbers Organism Play Post-Translational Protein Processing Promoter Regions Proteins RNA Interference RNA Polymerase II Regulation Research Research Personnel Research Proposals Role SAGA TAF1 gene TATA-Binding Protein Associated Factors TBP-Associated Factor 4 Therapeutic Transcriptional Activation Transcriptional Regulation base cell type chromatin immunoprecipitation design fly genetic regulatory protein human TAF1 protein human TAF2 protein human TAF5 protein human disease imaginal disc in vivo insight mutant novel prevent programs promoter research study transcription factor

项目摘要

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。