MECHANISMS OF YEAST TRANSCRIPTIONAL REGULATORS

描述(改编自调查人员摘要)：的长期目标 这个提议是用精确的分子术语来理解如何表达 在酿酒酵母中的一大组基因被Tup1/SSN6抑制因子抑制 很复杂。建议分为三个基本部分：(1) Tup1/SSN6转录抑制机制的确定 以及进行该过程所需的额外蛋白质的鉴定；(2) 以Tup1/SSN6为实验平台的通用计算机系统的研制 理解两个常见蛋白质基序WD40重复和TPR的模型； 以及(3)酵母中整个Tup1/SSN6调控网络的描述， 包括所有利用Tup1/SSn6和Tup1/SSn6的DNA结合蛋白 由每个DNA结合蛋白控制的一套完整的基因。这项建议 也涵盖了实验室的一个新的研究方向，CHD1的探索，一个 高度保守的酵母蛋白，可能在 染色质结构及其与转录的关系。 实验方法强调使用纯化的蛋白质和 生化实验，以推断分子机制。遗传方法 在酵母中也被用来测试从生化的 作为研究和探索的工具。DNA芯片和噬菌体展示 在特定情况下也会利用技术。 鉴于基因调控蛋白的高度保守性和 在所有真核生物中，似乎有可能 本文中介绍的酵母蛋白的许多原理 建议将适用于其他环境。对互联网的基本认识 作为细胞特化基础的分子事件不仅提供了 用于理解过程如何失败的框架，但也提供了 用于设计治疗策略的基础和知识 干预。

DESCRIPTION (adapted from investigator's abstract): The long-term goal of this proposal is to understand, in precise molecular terms, how expression of a large set of genes in S. cerevisiae is repressed by Tup1/Ssn6 repressor complex. The proposal is divided into three basic parts: (1) the determination of the mechanism of transcriptional repression by Tup1/Ssn6 and the identification of additional proteins required to carry it out; (2) the development, using Tup1/Ssn6 as the experimental system, of a general model for understanding two common protein motifs, the WD40 repeat and TPR; and (3) a description of the entire Tup1/Ssn6 regulatory network in yeast, including all the DNA-binding proteins that utilize Tup1/Ssn6 and the complete set of genes controlled by each DNA-binding protein. The proposal also covers a new research direction in the lab, an exploration of CHD1, a highly conserved yeast protein that likely serves an important function in chromatin structure and its relation to transcription. The experimental approaches emphasize the use of purified proteins and biochemical experiments to deduce molecular mechanisms. Genetic approaches in yeast are also utilized to test models developed from the biochemical studies and as exploratory tools. Finally DNA chip and phage display technologies are also utilized in specific cases. Given the high degree of conservation of gene regulatory proteins and general transcription factors among all eucaryotes, it seems likely that many of the principles developed for the yeast proteins covered in this proposal will apply in other settings. A basic understanding of the molecular events underlying cell specialization provides not only a framework for understanding how the process can fail, but also provides the substrates and knowledge to design therapeutic strategies based on intervention.