Mechanisms of Eukaryotic Gene Regulation

项目摘要/摘要 该研究计划的主要长期目标是了解RNA的调节机制。 聚合酶II在动物体内的转录。为什么研究基因表达如此重要？多样化的基础 一系列生物现象，包括许多人类疾病，可以追溯到适当的或不适当的 一个基因或一组基因的表达。因此，对基因表达机制的新见解将具有 对生物科学产生深远影响。将特别强调对RNA的研究 聚合酶II核心启动子，它是DNA的一小段，指导转录的启动。何以 研究核心启动子很重要吗？首先，核心启动子是“转录的门户”-- 导致转录启动的信号的汇聚。在这方面，核心推动者处于关键地位 在转录过程中的战略地位。第二，核心推动者是核心和不可或缺的组成部分 组成染色质(包括DNA)中的信号的RNA聚合酶II转录系统 序列基序)以及读取这些信号并执行转录过程的因子。目前， 核心启动子元件在人类以外的生物体中得到了最好的理解。人类核心推动者， 它很复杂，很难破译，这是下一个挑战。因此，未来的目标包括阐明 人类核心启动子的组成及其转录因子的鉴定和分析 具有特定序列元件的功能，以调节人类的基因表达。这部作品 应该为人类转录调控机制提供新的和重要的见解。一个 这项研究计划的第二个目标是了解染色质的各种功能--天然的 真核细胞中DNA的一种形式。因为DNA是遗传物质，因此 重要的是，人们对影响染色质和DNA的因素和机制有强烈和广泛的兴趣 结构和完整性。特别是，这些过程将在染色质和 DNA--也就是说，在染色质的背景下，而不仅仅是DNA。一个特别感兴趣的领域是 通过与核小体结合来保护DNA免受损伤的因子的研究。对保护环境的新见解 DNA对抗诸如活性氧之类的损害剂不仅提供了重要的基础 对细胞功能的了解，但也将与了解和预防癌症有关。

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.