Type B histone acetyltransferases and the assembly of chromatin structure

在此输入文本，它是应用程序的新摘要信息。本节必须是否 超过30行的文本。 当DNA复制时，染色质结构也必须复制。父母（Parent） 组蛋白被回收，然后在复制过程中在它们的原始位点附近重新组装。 住所因此，特定染色质结构域的表观遗传可以通过空间结构域来促进。 保留正确修饰的亲本组蛋白。然而，包装新复制的DNA需要 等量新合成的组蛋白的掺入。这使情况复杂化， 而不是作为一个空白的石板，这些特定的修改模式可以复制，新的 合成的组蛋白以精确的修饰模式组装。本提案的目的是 了解组蛋白乙酰转移酶Hat 1的功能，这是新的乙酰化所必需的。 合成组蛋白。该提案将重点关注Hat 1在组装和调节 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Hat 1 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。一个次级目标将 产生特异性阻断这些活性中的每一种的Hat 1突变，以鉴定Hat 1的功能， 这对于新合成的H3和H4的处理很重要。第二个子目标将利用亲和力 纯化新复制的DNA以鉴定新生染色质中Hat 1依赖性的变化。 该提案的第二个目标是确定Hat 1在线粒体功能中的作用。蛋白 已知乙酰化在线粒体活性的调节中起关键作用。然而，蛋白质 负责线粒体蛋白乙酰化的乙酰转移酶是完全未知的。我们有 发现Hat 1定位于线粒体，其目的是确定Hat 1在线粒体中的底物。 细胞器，并确定如何Hat 1依赖的线粒体乙酰化影响这个细胞器的功能。

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.