Mechanisms of transcription reinitiation

基因不仅为生物体的物理特征编码蓝图，而且还为每个细胞在正常条件下如何运作以及对各种刺激和环境的反应进行编码。为了使生物体正常发育和发挥功能，必须在正确的时间、在正确的水平、在正确的细胞中启动或“表达”适当的一组基因。当它们被表达时，由基因编码的指令在基因转录过程中被读取。我们感兴趣的是研究转录和调控基因表达的机制，这是细胞用来控制基因何时表达和表达到什么水平的方法。启动子是基因的一部分，在控制基因表达方面发挥着重要作用。几十年来进行的许多研究已经详细了解了一组称为转录因子的蛋白质是如何在基因启动子上组装，从而在适当的时间启动相关基因的。然而，我们对转录开始后与启动子结合的转录因子的情况知之甚少。也就是说，目前还不清楚细胞在第一次启动后如何继续表达基因。也不清楚细胞如何控制开启的基因的表达水平，或者当基因不再需要时如何关闭它们。我们研究计划的目的是研究与已经开启的基因启动子相关的转录因子的命运。以发芽酵母作为模式生物，我们将确定转录因子发生了哪些变化，从而允许基因通过多轮转录继续表达，这被称为转录重新启动。此外，我们将确定适当的细胞系统，允许转录因子从启动子中清除，以便在适当的时候关闭或停用基因。总体而言，我们的研究计划将识别和检查基因表达调控的新机制。我们希望我们的工作结果能够增加对基因最初是如何启动的相当详细的理解，从而提供更完整的基因表达图景。通过我们的工作，我们将探索每个基因如何工作的鲜为人知的但基本的方面，这些方面将对加拿大和世界各地的其他人在基因表达领域具有价值。

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.