Transcription Regulation by NC2

NC2 的转录调控

• 批准号: 6835150
• 负责人: DANNY REINBERG
• 金额: $ 22.53万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6835150
• 关键词: DNA directed RNA polymerase; enzyme mechanism; gene expression; gene induction /repression; genetic promoter element; genetic transcription; laboratory mouse; protein binding; transcription factor

DESCRIPTION (provided by applicant): The long-term goal of my laboratory is to formulate an understanding of the molecular mechanisms operating to regulate expression of class II genes. To this end, the overall aim of this proposal is to continue and expand studies now in progress on the mechanisms by which genes are maintained in a repressed state. This will be accomplished through the characterization of the proteins involved, and their various protein-DNA and protein-protein interactions. Studies on specific transcription of class II genes have indicated that most of the complexity and regulation of RNA synthesis catalyzed by RNA polymerase H probably resides in the initiation step - the recognition of promoter sequences. Proteins have been isolated that together can reconstitute specific transcription from many class I promoters. Much of the emphasis has been on the isolation of regulatory factors, such as activators. coactivators, repressors and corepressors. In most instances, the genes encoding these particular regulators, as well as all of the general transcription factors have been cloned. However, a description of the exact mechanisms controlling gene expression at the transcriptional level hinges on an understanding of this complex process mechanistically using physiological templates. The transcription field has now moved towards reconstituting transcription using chromatin templates. Our studies on promoter recognition by the general transcription factors of the RNA polymerase I transcription system, including repression and anti-repression, have broad implications for the mechanism of RNA synthesis in general and will provide the basis for understanding how specific transcription (actors can modify the transcriptional activity of a particular gene or a set of genes within the context of chromatin and/or using natural promoters. It is likely that these studies will yield basic principles from which the regulatory mechanisms of class II gene expression can be discerned at the molecular level. To this end, the overall aim of this proposal is to continue and expand studies on the mechanisms by which a specific repressor complex, NC2, composed of two subunits Dri and Drapi, operates to regulate gene expression. I propose studies using three different approaches. One approach is directed towards understanding the biochemical properties of the factor. The second approach is directed towards developing an understanding of the role of Dr1 and Drap1 in vivo, using a simple organism, yeast, with which we can apply genetics and study the relationships between Dr1 and Drap1 and other transcription factors. The third approach is directed towards formulating an understanding of the role of the factor in a multicellular organism and thus I describe studies in the mouse.

描述（由申请人提供）：我实验室的长期目标是 形成对调节分子机制的理解 II类基因的表达。为此，本提案的总体目标是 继续并扩大目前正在进行的关于基因作用机制的研究 都维持在压抑的状态。这将通过 所涉及蛋白质的表征及其各种蛋白质-DNA 和 蛋白质-蛋白质相互作用。 II类特异性转录的研究 基因表明RNA的大部分复杂性和调控 RNA聚合酶H催化的合成可能存在于起始步骤 - 启动子序列的识别。已分离出蛋白质 一起可以从许多 I 类启动子重建特异性转录。 大部分重点都放在监管因素的隔离上，例如 激活剂。共激活子、阻遏物和辅阻遏物。在大多数情况下， 编码这些特定调节因子以及所有一般调节因子的基因 转录因子已被克隆。然而，具体的描述 在转录水平上控制基因表达的机制取决于 利用生理学对这一复杂过程的机械理解 模板。转录领域现已走向重构 使用染色质模板进行转录。我们对启动子识别的研究 RNA聚合酶I转录系统的通用转录因子， 包括镇压和反镇压，对 RNA合成的一般机制，并将为以下方面提供基础： 了解特定的转录（参与者可以修改转录） 染色质背景下特定基因或一组基因的活性 和/或使用天然启动子。这些研究很可能会产生 II类基因调控机制的基本原理 表达可以在分子水平上辨别。为此，总体 该提案的目的是继续并扩大对机制的研究 其中一个特定的阻遏复合物 NC2，由两个亚基 Dri 和 Drapi 的作用是调节基因表达。我建议使用三个研究 不同的方法。一种方法旨在理解 该因子的生化特性。第二种方法是针对 使用以下方法了解 Dr1 和 Drap1 在体内的作用 简单的生物体，酵母，我们可以用它来应用遗传学并研究 Dr1和Drap1与其他转录因子之间的关系。第三个 方法的目的是形成对组织作用的理解 多细胞生物体中的一个因素，因此我描述了在小鼠中的研究。