Mechanisms of Eukaryotic Gene Regulation

真核基因调控机制

• 批准号: 10204661
• 负责人: James T. Kadonaga
• 金额: $ 69.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-18 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10204661
• 关键词: Affect; Animals; Area; Binding; Biological Phenomena; Biological Sciences; Cell Nucleus; Cell physiology; Chromatin; Chromatin Structure; Complex; DNA; DNA Damage; DNA Sequence; DNA Structure; Defect; Elements; Future; Gene Expression; Gene Expression Regulation; Genes; Genetic Materials; Genetic Transcription; Goals; Human; Knowledge; Lead; Malignant Neoplasms; Mediating; Molecular; Nucleosomes; Organism; Positioning Attribute; Process; RNA Polymerase II; Reactive Oxygen Species; Regulation; Research; Signal Transduction; Site; Stretching; System; Transcription Initiation; Transcription Process; Transcriptional Regulation; Work; cancer prevention; human disease; insight; interest; programs; promoter; transcription factor

Project Summary/Abstract The major long-term objective of this research program is to understand the mechanisms of regulation of RNA polymerase II transcription in animals. Why is it important to study gene expression? The basis of a diverse range of biological phenomena, including many human diseases, can be traced to the proper or improper expression of a gene or set of genes. Thus, new insights into the mechanisms of gene expression will have a far-reaching impact upon the biological sciences. Specific emphasis will be placed upon the study of the RNA polymerase II core promoter, which is the short stretch of DNA that directs the initiation of transcription. Why is it important to study the core promoter? First, the core promoter is the "gateway to transcription" – the site of convergence of the signals that lead to transcription initiation. In this regard, the core promoter is at a key strategic position in the transcription process. Second, the core promoter is a central and integral component of the RNA polymerase II transcription system that comprises the signals in the chromatin (including DNA sequence motifs) and the factors that read those signals and carry out the transcription process. At present, core promoter elements are best understood in organisms other than humans. The human core promoter, which is complex and difficult to decipher, is the next challenge. Hence, future goals include the elucidation of the components of the human core promoter and the identification and analysis of the transcription factors that function with specific sequence elements to mediate the regulation of gene expression in humans. This work should provide new and important insights into the mechanisms of transcriptional regulation in humans. A second objective of this research program is to understand the diverse functions of chromatin – the natural form of DNA in the eukaryotic nucleus. Because DNA is the genetic material and is thus of the utmost importance, there is a strong and broad interest in the factors and mechanisms that affect chromatin and DNA structure and integrity. In particular, these processes will be investigated at the interface of chromatin and DNA – that is, in the context of chromatin rather than with DNA alone. One particular area of interest is the study of factors that protect DNA from damage by binding to nucleosomes. New insights into the protection of DNA against damaging agents such as reactive oxygen species would not only provide important fundamental knowledge of cellular function, but would also be relevant to the understanding and prevention of cancer.

项目摘要/摘要 该研究计划的主要长期目标是了解RNA调节的机制 动物中的聚合酶II转录。为什么研究基因表达很重要？潜水者的基础 包括许多人类疾病在内的一系列生物现象可以追溯到适当或不当 基因或一组基因的表达。这，对基因表达机制的新见解将具有 对生物科学的影响深远。将重点放在RNA的研究上 聚合酶II核心启动子，这是指导转录倡议的简短DNA。为什么是 研究核心启动子是否重要？首先，核心启动子是“转录门户” - 导致转录启动的信号的收敛。在这方面，核心促进者是关键 在转录过程中的战略位置。其次，核心启动子是中心组成部分 RNA聚合酶II转录系统的包含染色质中的信号（包括DNA） 序列主题）以及读取这些信号并执行转录过程的因素。现在， 除人类以外的生物体中，最好理解核心启动子元素。人核心促进者， 这是复杂且难以破译的，这是下一个挑战。因此，未来的目标包括阐明 人核启动子的组成部分以及对转录因子的识别和分析 具有特定序列元素的功能，可以介导人类基因表达的调节。这项工作 应提供有关人类转录调节机制的新的重要见解。一个 该研究计划的第二个目标是了解染色质的潜水功能 - 自然 真核核中DNA的形式。因为DNA是遗传物质，因此是最大的 重要的是，对影响染色质和DNA的因素和机制有着强烈而广泛的兴趣 结构和完整性。特别是，这些过程将在染色质的界面和 DNA - 也就是说，在染色质而不是单独使用DNA的情况下。感兴趣的一个特定领域是 研究通过与核小体结合来保护DNA免受损伤的因素。对保护的新见解 针对破坏性剂（例如活性氧）的DNA不仅提供重要的基本 对细胞功能的了解，但也与对癌症的理解和预防有关。