权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Characterization of Type B Histone Acetyltransferases

B 型组蛋白乙酰转移酶的表征

基本信息

批准号：
6636629
负责人：
MARK R PARTHUN
金额：
$ 24.49万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-07-01 至 2006-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (Verbatim from the applicant's abstract): Chromatin is the nucleoprotein structure that enables chromosomal DNA to be condensed and packaged in eukaryotic nuclei. The primary protein components of chromatin are the core histones (H2A, H2B, H3, and H4). Chromatin structure plays an active role in the regulation of many cellular processes that involve accessing chromosomal DNA, such as transcription, DNA replication, recombination and DNA repair. As the regulation of many aspects of normal cell growth requires the tight control of these processes, it is important to understand how they are influenced by, and interact with, chromatin structure. Much of the regulatory potential of the core histones resides small, positively charged domains called the NH2-terminal tails. The core histone NH2-terminal tails are subject to a wide range of post-translational modifications, of which acetylation is the most extensively characterized. The acetylation of histones, which appears to be a fundamental mechanism by which cells regulate chromatin structure, occurs on lysine residues, negating their positive charge. The acetylation state of the histones is governed by the interplay of enzymes that add acetyl groups (histone acetyltransf erases) and enzymes that remove them (histone deacetylases). Histone acetyltransferases can be divided into two classes based on substrate specificity and cellular localization. Type A histone acetyltransferases are nuclear enzymes that acetylate histones in a chromatin context. Type B histone acetyltransferases acetylate free histones and can be found in the cytoplasm. While type A histone acetyltransferases, such asGcn5p, have been conclusively linked to the regulation of gene expression, little is known about the function of type B histone acetyltransferases. However, using the yeast type B histone acetyltransferase Hat1 p as a model, we have recently obtained evidence that these enzymes are involved in silent chromatin structure and DNA damage repair. The primary goal of our research is to extend these results, using a combination of molecular genetics and biochemistry, to define the in vivo role of type B histone acetyltransferases. This goal will be pursued through three specific aims. The first is to determine the mechanism(s) through which Hat1p affects the silent chromatin structure found near yeast telomeres. The second is to characterize the involvement of Hat1p and chromatin structure the repair of DNA double strand breaks. Third, we will isolate and characterize novel type B histone acetyltransferases.

描述（逐字摘自申请人的摘要）：染色质是使染色体 DNA 能够浓缩并包装在真核细胞核中的核蛋白结构。染色质的主要蛋白质成分是核心组蛋白（H2A、H2B、H3 和 H4）。染色质结构发挥着积极作用在许多涉及访问的细胞过程的调节中发挥作用染色体DNA，例如转录、DNA复制、重组和DNA 维修。由于正常细胞生长的许多方面的调节需要严格控制这些过程，了解它们是如何进行的很重要受染色质结构影响并与之相互作用。大部分监管核心组蛋白的潜力存在于小的、带正电的区域，称为 NH2 末端尾部。核心组蛋白 NH2 末端尾部受到广泛的翻译后修饰，其中乙酰化是最重要的最广泛的特征。组蛋白的乙酰化，这似乎是细胞调节染色质结构的基本机制赖氨酸残基上，消除其正电荷。乙酰化状态组蛋白受添加乙酰基的酶的相互作用控制（组蛋白乙酰转移酶）和去除它们的酶（组蛋白脱乙酰酶）。组蛋白乙酰转移酶可分为两类底物特异性和细胞定位。 A型组蛋白乙酰转移酶是乙酰化染色质中组蛋白的核酶语境。 B 型组蛋白乙酰转移酶乙酰化游离组蛋白，并且可以发现于细胞质中。而 A 型组蛋白乙酰转移酶，如 Gcn5p，已最终确定与基因表达的调控有关，但很少有已知 B 型组蛋白乙酰转移酶的功能。然而，使用以酵母 B 型组蛋白乙酰转移酶 Hat1 p 作为模型，我们最近获得证据表明这些酶参与沉默染色质结构和DNA损伤修复。我们研究的主要目标是扩展这些结果，结合分子遗传学和生物化学，定义 B 型组蛋白乙酰转移酶的体内作用。这个目标将是通过三个具体目标来实现。首先是确定机制 Hat1p 通过它影响酵母附近发现的沉默染色质结构端粒。第二个是表征Hat1p和染色质的参与构建DNA双链断裂的修复。第三，我们将隔离并表征新型 B 型组蛋白乙酰转移酶。