Mechanisms of transcription reinitiation

基因不仅为生物体的物理特征编码蓝图，而且还指示每个细胞在正常条件下以及对各种刺激和环境的反应应该如何发挥作用。一个有机体要正常发育和运作，就必须在正确的时间、正确的水平和正确的细胞中，开启或“表达”一组适当的基因。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，在控制基因表达中起主要作用。几十年来进行的许多研究已经详细了解了一组被称为转录因子的蛋白质是如何聚集在基因启动子上，在适当的时候打开相关基因的。然而，我们对转录开始后与启动子结合的转录因子发生了什么知之甚少。也就是说，尚不清楚细胞在首次启动后如何继续表达基因。也不清楚细胞是如何控制基因的表达水平的，或者当基因不再需要时是如何关闭的。我们的研究计划的目的集中在研究与基因启动子相关的转录因子的命运。使用出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，这被称为转录再起始。此外，我们还将确定允许转录因子从启动子中清除的细胞系统，以便在适当的时候关闭或使基因失活。总的来说，我们的研究计划将确定和检查基因表达调节的新机制。我们希望我们的工作结果能够增加对基因最初是如何开启的相当详细的理解，从而提供一个更完整的基因表达图像。通过我们的工作，我们将探索每个基因如何工作的基本方面，这将对加拿大和世界各地的基因表达领域的其他人有价值。

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.