Gene Regulation and Control of Chromatin Structure by Abf1 and Rap1

Rap1和Abf1是酵母中具有转录激活和抑制、复制和端粒结构等功能的一般调控因子（GRFs）。这两种GRFs都具有创建开放染色质局部区域的能力，可以促进其他激活因子与基因启动子的结合，从而促进基因激活。然而，这两个GRFs在某些方面也有所不同。最引人注目的是，Rap1的持续结合是促进持续转录激活所必需的，而Abf1结合的丧失（使用Abf1 -1 - ts突变体）不会导致转录减少。因此，至少一些启动子保留了Abf1结合的“记忆”。在这个项目中，Rap1和Abf1促进转录激活和扰乱局部染色质结构的机制，以及这种“记忆效应”的基础，将通过生物化学、遗传学和基因组学方法的结合获得新的见解。基因激活取决于特定转录因子与基因启动子的结合。在这个项目中，两个这样的因子，Abf1和Rap1，作为“一般调节因子”，通过协助酵母中许多基因的激活将被研究。这些研究将包括生物化学、遗传学和基因组学方法，以了解这两个因素促进转录激活的机制，包括它们对基因启动子包装成染色质的影响。这项工作的结果将提供可能适用于所有真核生物的新信息，因为转录机制是高度保守的。这些调查将包括本科生参与的夏季研究，并将产生可供科学界使用的基因组数据。

Rap1 and Abf1 are General Regulatory Factors (GRFs) that function in transcriptional activation and repression, replication, and telomere structure in yeast. These two GRFs share an ability to create a local region of open chromatin which can facilitate binding of other activators to gene promoters and thus contribute to gene activation. However, these two GRFs also differ in some respects. Most dramatically, continued binding of Rap1 is required to facilitate ongoing transcriptional activation, whereas loss of Abf1 binding (using an abf1-1 ts mutant) does not result in decreased transcription. Thus, at least some promoters retain a "memory" of Abf1 binding. In this project, new insight into the mechanism by which Rap1 and Abf1 contribute to transcriptional activation and perturb local chromatin structure, and into the basis of this "memory effect," will be obtained using a combination of biochemical, genetic, and genomic approaches.Gene activation depends on binding of specific transcription factors to gene promoters. In this project, two such factors, Abf1 and Rap1, that operate as "General Regulatory Factors" by assisting in activation of many genes in yeast will be investigated. The studies will include biochemical, genetic and genomic approaches to understanding the mechanism by which these two factors contribute to transcriptional activation, including their effects on the packaging of gene promoters into chromatin. The results of this work will provide new information that is likely to apply to all eukaryotes, as the transcription machinery is highly conserved. These investigations will include participation by undergraduates conducting summer research, and will yield genomic data that will be made available to the scientific community.