Type B histone acetyltransferases and the assembly of chromatin structure

B型组蛋白乙酰转移酶和染色质结构的组装

• 批准号: 8887576
• 负责人: MARK R PARTHUN
• 金额: $ 35.74万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8887576
• 关键词: Acetylation; Acetyltransferase; Address; Affect; Affinity Chromatography; Animal Model; Animals; Area; Cell Proliferation; Cell physiology; Cells; Chromatin; Chromatin Modeling; Chromatin Structure; Complex; Coupled; DNA; DNA Double Strand Break; DNA biosynthesis; Data; Defect; Development; Disease; Enzymes; Epigenetic Process; Funding; Goals; Heterochromatin; Histone H3; Histone H4; Histones; In Vitro; Knockout Mice; Laboratories; Lysine; Mammalian Cell; Metabolism; Mitochondria; Mitochondrial Proteins; Modeling; Modification; Molecular Chaperones; Mus; Mutation; Neonatal; Organelles; Pattern; Play; Process; Protein Acetylation; Proteins; Proteomics; Recycling; Regulation; Role; Site; Structure; System; Testing; Text; Yeasts; abstracting; base; histone acetyltransferase; histone modification; novel; recombinational repair; residence

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. When DNA is replicated, the chromatin structure must be duplicated, as well. The pre-existing (or parental) histones are recycled and then reassembled following the passage of the replication near their original site of residence. Hence, the epigenetic inheritance of a specific chromatin domain can be facilitated by the spatial retention of the correctly modified parental histones. However, packaging of the newly replicated DNA requires the incorporation of an equal quantity of newly synthesized histones. This complicates the situation as, rather than being a blank slate upon which these specific patterns of modification can be reproduced, the newly synthesized histones are assembled with precise patterns of modification. The goal of this proposal is to understand the function of the histone acetyltransferase Hat1, which is necessary for the acetylation of newly synthesized histones. This proposal will focus on the function of Hat1 in the assembly and regulation of chromatin structure, as well as other aspects of cell metabolism. The first specific aim will use a variety of in vitro analyses to examine the mechanisms by which Hat1 influences the modification of newly synthesized histones and replication-coupled chromatin assembly. Hat1- containing complexes have both histone acetyltransferase and histone chaperone activities. One sub-aim will generate Hat1 mutations that specifically block each of these activities to identify the functions of Hat1 that are important for the processing of newly synthesized H3 and H4. A second sub-aim will employ affinity purification of newly replicated DNA to identify Hat1-dependent changes in nascent chromatin. The goal of the second aim of this proposal is to determine the role of Hat1 in mitochondrial function. Protein acetylation is known to play a critical role in the regulation of mitochondrial activity. However, the protein acetyltransferases responsible for the acetylation of mitochondrial proteins are completely unknown. We have found that Hat1 is localized to mitochondria and the goal of this aim is to identify substrates of hat1 in this organelle and determine how Hat1-dependent mitochondrial acetylation affects the function of this organelle.

在此处输入文本，该文本是您的应用程序的新摘要信息。此部分必须没有 文本长度超过 30 行。 当DNA复制时，染色质结构也必须复制。先前存在的（或父母的） 组蛋白被回收，然后在其原始位点附近的复制通过后重新组装 住宅。因此，特定染色质结构域的表观遗传可以通过空间 保留正确修饰的亲本组蛋白。然而，包装新复制的 DNA 需要 掺入等量的新合成的组蛋白。这使情况变得复杂，因为 与可以在其上复制这些特定修改模式的白板相比，新的 合成的组蛋白以精确的修饰模式组装。该提案的目标是 了解组蛋白乙酰转移酶 Hat1 的功能，这对于新的乙酰化是必需的 合成组蛋白。该提案将重点关注Hat1在组装和监管中的功能 染色质结构以及细胞代谢的其他方面。 第一个具体目标将使用各种体外分析来检查 Hat1 的机制 影响新合成的组蛋白的修饰和复制偶联染色质组装。帽子1- 含有复合物同时具有组蛋白乙酰转移酶和组蛋白伴侣活性。一个子目标将 生成专门阻止这些活动的 Hat1 突变，以确定 Hat1 的功能 对于新合成的 H3 和 H4 的加工很重要。第二个子目标将利用亲和力 纯化新复制的 DNA，以识别新生染色质中依赖 Hat1 的变化。 该提案的第二个目标是确定 Hat1 在线粒体功能中的作用。蛋白质 已知乙酰化在线粒体活性的调节中发挥关键作用。然而，蛋白质 负责线粒体蛋白质乙酰化的乙酰转移酶是完全未知的。我们有 发现 Hat1 定位于线粒体，该目的的目标是确定 hat1 在线粒体中的底物 细胞器并确定 Hat1 依赖性线粒体乙酰化如何影响该细胞器的功能。