EUKARYOTIC GENE REGULATION AS STUDIED IN YEAST

复杂的基因调控模式是高等动物发展的基础 生物体和许多已知的疾病都与异常基因有关 监管。 所提出的实验旨在发现基本原理 基因调控机制。 为此，主要提出研究 与酵母和哺乳动物细胞；前者强调利用遗传学 与生物化学相结合，以及使用不同的生物体 允许测试任何给定发现的普遍性。 建议 创建和研究绕过普通转录激活剂 转录激活区域的要求。 将会被测试 这些“非经典”聚合酶激活剂是否非常有效 通过形成 RNA 聚合酶 II 的一部分，在酵母中发挥强大作用 全酶并将该结构招募到 DNA 中。 这些实验将 与经典激活剂的实验平行，这些实验将尝试 识别转录激活区域的靶标并确定 激活区域-靶标相互作用是否通过以下方式触发基因激活 全酶招募。 对这两类的进一步实验 激活器将用于区分模型的具体情况 抑制器起作用。 核小体在帮助和阻碍基因中的作用 将使用这两类激活剂来分析激活；和 克服核小体抑制作用的机制 探索过。

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.