Mechanisms of transcription reinitiation

转录重新启动的机制

• 批准号: RGPIN-2014-04208
• 负责人: Rosonina, Emanuel
• 金额: $ 2.91万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629872
• 关键词: Mechanisms; transcription; reinitiation

Genes encode blueprints not only for physical traits of organisms, but also instructions on how each cell should function in normal conditions and in response to a variety of stimuli and environments. For an organism to develop and function properly, the appropriate set of genes must be turned on, or “expressed,” at the correct time, at the correct level, and in the correct cells. When they are expressed, the instructions encoded by genes are read through the process of gene transcription. We are interested in studying transcription and mechanisms of regulating gene expression, which are methods used by cells to control when genes are expressed and to what level. Promoters are portions of genes that play a major role in controlling gene expression. Many studies performed over several decades have led to a detailed understanding of how a set of proteins, called transcription factors, assemble at gene promoters to turn on the associated genes at the appropriate time. We know very little, however, about what happens to the transcription factors that are bound to promoters once transcription has begun. That is, it is not clear how cells continue to express genes after they have first been turned on. Nor is it clear how cells control the level of expression of genes that are turned on, or how genes are shut off when they are no longer needed.The aims of our research program focus on studying the fate of transcription factors associated with promoters of genes that have been turned on. Using budding yeast as a model organism, we will determine what changes to transcription factors take place that allow continued expression of genes through multiple rounds of transcription, which is referred to as transcriptional reinitiation. Additionally, we will identify cellular systems that are in place that allow transcription factors to be cleared from promoters in order to shut down, or deactivate, genes when appropriate. Overall, our research program will identify and examine novel mechanisms by which gene expression is regulated. We expect the results of our work to add to the considerably detailed understanding of how genes are first turned on, thereby providing a more complete picture of gene expression. Through our work, we will be exploring poorly understood, yet fundamental aspects of how every gene works that will be valuable to others in Canada and around the world in the gene expression field.

基因不仅编码生物体物理特征的蓝图，还编码每个细胞在正常条件下如何发挥作用以及响应各种刺激和环境的指令。为了使有机体正常发育和发挥功能，必须在正确的时间、以正确的水平、在正确的细胞中开启或“表达”适当的基因组。当它们被表达时，基因编码的指令通过基因转录的过程被读取。我们感兴趣的是研究转录和调节基因表达的机制，这是细胞用来控制基因何时表达以及表达到什么水平的方法。启动子是在控制基因表达中起主要作用的基因部分。几十年来进行的许多研究已经使人们详细了解了一组称为转录因子的蛋白质如何在基因启动子处组装以在适当的时间打开相关基因。然而，我们对转录开始后与启动子结合的转录因子会发生什么知之甚少。也就是说，尚不清楚细胞在首次启动后如何继续表达基因。我们也不清楚细胞如何控制打开的基因的表达水平，或者基因在不再需要时如何关闭。我们研究计划的目标是研究与已打开的基因启动子相关的转录因子的命运。使用芽殖酵母作为模型生物，我们将确定转录因子发生哪些变化，从而允许基因通过多轮转录持续表达，这被称为转录重新启动。此外，我们将确定允许从启动子中清除转录因子的细胞系统，以便在适当的时候关闭或失活基因。总体而言，我们的研究计划将确定并检查基因表达调节的新机制。我们期望我们的工作结果能够增加对基因如何首次开启的相当详细的理解，从而提供基因表达的更完整的图景。通过我们的工作，我们将探索每个基因如何发挥作用的鲜为人知但基本的方面，这对于加拿大和世界各地基因表达领域的其他人来说都是有价值的。