Mechanisms of Transcriptional Regulation in Eukaryotes

真核生物转录调控机制

• 批准号: 8387752
• 负责人: James T. Kadonaga
• 金额: $ 32.51万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8387752
• 关键词: Anterior; Biological; Biological Factors; Complex; DNA Sequence; Development; Dorsal; Drosophila genus; Elements; Embryo; Eukaryota; Future; Gene Expression; Gene Expression Regulation; Gene Family; Generic Drugs; Genes; Genetic Transcription; Goals; Grant; Human; Indium; Knowledge; Lead; Malignant Neoplasms; Molecular; Pattern; Property; Proteins; RNA Interference; RNA Polymerase II; Regulation; Regulatory Element; Research; Role; System; TATA Box; Time; Transcription Initiation; Transcription Process; Transcriptional Regulation; Transgenic Organisms; base; enhancer binding protein; human disease; insight; novel; overexpression; promoter; public health relevance; transcription factor

DESCRIPTION (provided by applicant): The long-term goal of this project is to uncover the role of the core promoter in the regulation of transcription by RNA polymerase II. The core promoter has been traditionally defined to be the sequences that direct the accurate initiation of transcription. However, this simple definition belies a complex and diverse component of the transcription process. Although the core promoter has historically been considered to be a somewhat generic and homogeneous moiety, it is now apparent that many different sequence motifs, such as the BREu, TATA, Inr, and DPE, can each confer specific transcriptional properties to the core promoter. There are no universal core promoter motifs. Moreover, in humans, the best known core promoter element, the TATA box, is present in only about 15% of promoters. It is thus likely that many more core promoter motifs remain to be discovered and characterized. The objective of the proposed research is to undertake a three-tiered approach to the study of the core promoter at the levels of DNA sequences, protein factors, and biological networks. Specific Aim 1 focuses upon the discovery of new core promoter elements. At the present time, there is an incomplete understanding of the DNA sequences that direct the initiation of transcription by RNA polymerase II. There are new motifs as well as transcriptional strategies that remain to be uncovered. Specific Aim 2 involves the identification and characterization of transcription factors that function in a core-promoter-specific manner. For example, Caudal is an enhancer-binding protein and master developmental regulator that functions as a DPE- specific activator. There are likely to be many other factors that regulate transcription via the core promoter. Specific Aim 3 will explore the function of specific core promoter motifs in biological networks. For instance, the DPE is a central component of the Hox gene system. It is likely that other gene networks employ specific core promoter motifs in their regulation. In the future, the core promoter will be an integral part of all analyses of transcriptional regulation. A key aim of this grant is to provide new and important insights into the core promoter and thus contribute critical knowledge for understanding how genes are regulated.

描述（由申请人提供）：该项目的长期目标是揭示核心启动子在RNA聚合酶II调节转录中的作用。传统上，核心启动子被定义为指导转录准确启动的序列。但是，这个简单的定义掩盖了转录过程中复杂而多样的组成部分。尽管从历史上看，核心启动子被认为是一个有点通用和均匀的部分，但现在很明显，例如BREU，TATA，INR和DPE等许多不同的序列主题可以将特定的转录特性赋予核心启动子。没有通用核心启动子图案。此外，在人类中，最著名的核心启动子元素tata盒仅存在于约15％的启动子中。因此，可能还有更多核心启动子图案有待发现和表征。拟议的研究的目的是在DNA序列，蛋白质因子和生物网络的水平上采用三层方法来研究核心启动子。特定目标1专注于发现新的核心启动子元素。目前，对指导RNA聚合酶II转录启动的DNA序列有不完全理解。有一些新的图案以及转录策略仍有待发现。特定的目标2涉及以核心促销特定方式起作用的转录因子的识别和表征。例如，尾尾是一种增强子结合蛋白和主要发育调节剂，可作为DPE-特异性激活剂。可能还有许多其他因素通过核心启动子来调节转录。特定的目标3将探索生物网络中特定核心启动子基序的功能。例如，DPE是HOX基因系统的核心组成部分。其他基因网络可能在其调节中采用特定的核心启动子图案。将来，核心启动子将是所有转录调节分析的组成部分。这笔赠款的主要目的是为核心促进者提供新的重要见解，从而为了解基因的调节方式提供批判知识。