IDENTIFICATION AND ANALYSIS OF HAT/COACTIVATOR COMPLEXES

帽子/共激活剂复合物的鉴定和分析

• 批准号: 6228328
• 负责人: PATRICK A GRANT
• 金额: $ 21.63万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6228328
• 关键词: acyltransferase; enzyme complex; gene expression; genetic manipulation; genetic promoter element; immunoprecipitation; intermolecular interaction; mutant; protein protein interaction; protein purification; protein structure function; transcription factor; yeasts

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.

描述（来自应用程序）：在真核细胞核中，DNA是 由组蛋白包装成核小体，即染色质的重复亚基。的 从染色质调节基因表达需要以下协同作用： 基因特异性激活和阻遏蛋白，一般转录因子 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基转移酶（HAT 在组蛋白的尾部。HAT活动经常被发现与 含有具有同一性的组分的大的多蛋白质辅活化剂复合物 或与已知的转录调节子同源。这些观测 为组蛋白乙酰化偶联提供了直接的分子基础， 转录的调节。乙酰化修饰染色质 被认为在病毒感染的病因学中起核心作用， 癌症和核激素受体作用机制。HAT/辅活化剂 已知蛋白质与细胞癌蛋白和肿瘤抑制蛋白相关， 蛋白质，并已被描述在某些易位相关 白血病 这项提案的目标是了解生物化学机制， 天然组蛋白乙酰转移酶/辅激活因子复合物的独特功能。 该建议的重点是一个新的酵母乙酰转移酶复合物命名为SLIK （SAGA样），在组成上与保守的佐贺HAT/辅激活因子相关 活动这种复合体的鉴定使某些遗传学复杂化， Ada，Spt和TAFII蛋白功能的解释以前归因于 佐贺。该提案的主要目标包括1。纯化及 识别SLIK组件，2.的功能表征 单个复合亚基，和3.启动子和基因特异性分析 佐贺和SLIK复合物。这些研究旨在揭示以下因素的潜在作用 不同的佐贺形式在不同的激活途径。