Eukaryotic Gene Regulation As Studied In Yeast

描述(申请人提供)：基因表达调控是基础 许多基本的生物过程，包括生物体的发育 从受精卵中，有机体对细胞外信号的反应，以及 记忆的根深蒂固。基因调控异常往往会导致 疾病状态，包括癌症。这笔赠款要求资金进行分析 基因调控的基本机制，将帮助我们理解 正常的过程，并阐明了它们如何会出错。建议进行的研究 使用酵母和哺乳动物细胞，这两种真核细胞中都有许多方面的基因 监管是密切相关的。需要解决的一般问题包括： 与DNA结合的基因激活物如何与其基因沟通 转录被激活；如何设计和测试合成的小基因 激活剂；如何天然的‘激活区’(当 与DNA捆绑在一起，与转录机制相互作用，激活 转录)可以被与转录因子相互作用的蛋白质所取代 转录机器以一种根本性的不同和揭示的方式； 如何分离新的转录激活肽以及它们如何 工作；一旦特定的抑制子与DNA捆绑在一起，如何抵消 激活剂；如何出现转录的各个比特 机械，在激活后的启动子，可以被精确分析；以及， 一般来说，酶(例如，负责转录的RNA聚合酶)如何 基因，以及在转录机制中发现的细胞周期蛋白依赖的激酶) 以一种特定的方式发挥作用，选择一个或另一个潜能 在任何指定的一组情况下都是目标。

DESCRIPTION (provided by applicant): Regulation of gene expression underlies many fundamental biological processes, including development of an organism from a fertilized egg, the response of organisms to extra-cellular signals, and the ingraining of memories. Very often aberrant gene regulation leads to diseased states, including cancer. This grant requests funds to pursue analyses of fundamental mechanisms of gene regulation that will help us understand the normal processes and shed light on how they can go awry. The proposed studies use yeast and mammalian cells, both eukaryotes in which many aspects of gene regulation are closely related. Among the general issues to be addressed are: how gene 'activators," bound to DNA, communicate with the genes whose transcription is activated; how to design and test small synthetic gene activators; how natural 'activating regions" (peptide sequences that when tethered to DNA interact with the transcriptional machinery to activate transcription) can be replaced by proteins that interact with the transcriptional machinery in a fundamental different, and revealing, fashion; how novel transcriptional activating peptides can be isolated and how they work; how a specific repressor, once tethered to DNA, counteracts the effect of activators; how the appearance of various bits of the transcriptional machinery, at a promoter following activation, can be precisely analyzed; and, in general, how enzymes (e.g. the RNA polymerase responsible for transcribing genes, and a cyclin-dependent kinase found in the transcriptional machinery) are made to function in a specific fashion, selecting one vs another potential target under any specified set of circumstances.