EUKARYOTIC GENE REGULATION AS STUDIED IN YEAST

基因调控的复杂模式是高等植物发育的基础 许多已知的疾病都与异常基因有关， 调控 所提出的实验旨在发现基本的 基因调控机制。 为此，主要提出了研究 酵母和哺乳动物细胞;前者强调遗传学的使用 与生物化学相结合， 允许测试任何给定发现的一般性。 拟 创造和研究转录激活因子， 转录激活区的要求。 它将受到考验 这些“非经典”聚合酶激活剂， 在酵母中，通过形成RNA聚合酶II的一部分来实现 全酶并将该结构补充到DNA中。 这些实验将 通过经典活化剂的实验， 鉴定转录激活区的靶标，并确定 激活区域-靶相互作用是否通过 全酶募集 用两种类型的 激活器将用于区分模型， 抑制剂起作用。 核小体在助基因和阻基因中的作用 激活将使用这两类激活剂进行分析; 克服核小体抑制作用的机制将是 探讨了

Complicated patterns of gene regulation underlie development of higher organisms, and many known diseases are associated with aberrant gene regulation. The proposed experiments are designed to discover fundamental mechanisms of gene regulation. To this end studies are proposed primarily with yeast and mammalian cells; the former emphasize the use of genetics in combination with biochemistry, and the use of disparate organisms allows the generality of any given discovery to be tested. It is proposed to create and study transcriptional activators that bypass the ordinary requirements for transcriptional activating regions. It will be tested whether these "non-classical" polymerase activators, which work extremely powerfully in yeast, do so by forming part of the RNA polymerase II holoenzyme and recruit that structure to DNA. These experiments will be paralleled by experiments with classical activators that will attempt to identify targets of transcriptional activating regions and to determine whether activating region-target interactions trigger gene activation by holoenzyme recruitment. Further experiments with both classes of activators will be used to distinguish between models for how specific repressors work. The role of nucleosomes in helping and hindering gene activation will be analyzed using these two classes of activators; and the mechanism of overcoming the inhibitory effect of nucleosomes will be explored.