IDENTIFICATION AND ANALYSIS OF HAT/COACTIVATOR COMPLEXES

描述(来自申请)：在真核细胞核中，DNA是 由组蛋白包装成核小体，核小体是染色质的重复亚单位。这个 染色质基因表达的调控需要多种基因的协同作用 基因特异性激活和抑制蛋白，通用转录因子 和染色质修饰活性。这些酶包括组蛋白 乙酰化高度保守的赖氨酸残基的乙酰转移酶(HATS) 在组蛋白的尾巴中。帽子活动经常被发现与 包含具有相同特性的组件的大型多蛋白共激活复合体 或与已知的转录调控因子同源。这些观察结果已经 为组蛋白乙酰化与组蛋白的偶联提供了直接的分子基础 转录的调节。染色质的乙酰化修饰 被认为在病毒感染的病因学中发挥核心作用 肿瘤及其核激素受体作用机制的研究。HAT/助激活剂 已知蛋白质与细胞癌蛋白和肿瘤抑制因子有关 蛋白质，并已在某些移位中被描述与 白血病。 这项建议的目标是了解生化机制和 天然组蛋白乙酰转移酶/辅活化子复合体的独特功能。 本提案的重点是一种名为SLIK的新型酵母乙酰转移酶复合体 (类似佐贺的)，在组成上与保守的佐贺帽子/共激活剂相关 活动。这种复合体的鉴定使某些基因变得复杂 对AdA、SPT和TAFII蛋白功能的解释 传奇故事。这项建议的主要目标包括1.提纯和 SLIK组分的鉴定，2.对其功能的表征 单个复合亚单位；3.启动子和基因特异性分析 佐贺和SLIK复合体。这些研究的目的是揭示 不同的激活途径形成不同的SAGA。

DESCRIPTION (from the application): In the eukaryotic cell nucleus, DNA is packaged by histones into nucleosomes, the repeating subunits of chromatin. The regulation of gene expression from chromatin requires the concerted action of gene specific activator and repressor proteins, general transcription factors and chromatin modifying activities. These enzymes include histone acetlytransferases (HATs) which acetylate the highly conserved lysine residues within histone tails. HAT activities are often found to be associated with large multiprotein coactivator complexes that contain components with identity or homology to known regulators of transcription. These observations have provided a direct molecular basis for the coupling of histone acetylation and the regulation of transcription. The modification of chromatin by acetylation is postulated to play a central role in the etiology of viral infection and cancer and in mechanism of nuclear hormone receptor action. HAT/coactivator proteins are known to associate with cellular oncoproteins and tumor suppressor proteins and have been described in certain translocations associated with leukemias. The goals of this proposal are to understand the biochemical mechanisms and unique functions of native histone acetyltransferase/coactivator complexes. This proposal focuses on a novel yeast acetyltransferase complex named SLIK (SAGA-Like), related in composition to the conserved SAGA HAT/coactivator activity. The identification of this complex has complicated certain genetic interpretations of Ada, Spt and TAFII protein function previously attributed to SAGA. The primary goals of this proposal include 1. Purification and identification of SLIK components, 2. Characterization of the function of individual complex subunits, and 3. Analysis of promoter and gene specificity of SAGA and SLIK complexes. These studies aim to reveal the potential roles of distinct SAGA forms in different activation pathways.