EUKARYOTIC GENE REGULATION AS STUDIED IN YEAST

复杂的基因调控模式是高等教育发展的基础 生物体，许多已知的疾病都与基因异常有关 监管。拟议的实验旨在发现基本的 基因调控机制。为此，初步提出了研究建议 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，使用完全不同的有机体 允许对任何给定发现的一般性进行测试。有建议说 创造和研究绕过普通基因的转录激活子 转录激活区的要求。它将接受测试 这些“非经典的”聚合酶激活剂，它们非常有效 在酵母中，通过形成RNA聚合酶II的一部分来实现这一点 全酶并将该结构招募到DNA中。这些实验将是 与经典激活剂的实验平行，这些实验将试图 确定转录激活区的靶点并确定 激活区域-靶相互作用是否通过以下方式触发基因激活 全酶招募。对这两个类别的进一步实验 激活器将用于区分不同型号的具体程度 抑制器起作用。核小体在基因帮助和阻碍中的作用 将使用这两类激活剂分析激活；以及 克服核小体抑制作用的机制将是 探索过了。

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.