REGULATION OF HISTONE GENE EXPRESSION IN MAMMALS

组蛋白是染色质中的主要蛋白质，起包装作用 将DNA转化为核小体结构。最近的 各种变种和修饰品的表征 在时间和空间上受调节的组蛋白具有 暗示这些蛋白质参与了基因表达的控制 分化和衰老。这项提议的最终目的是 为了确定组蛋白基因的分子机制 是如此不同的监管，以便处理问题 关于这些蛋白质的功能。这将会实现 通过详细的分析，转录，翻译，和 时间调控组蛋白H3亚型中的两个成员。 将特别注意详细的分子 这些基因及其mRNAs的结构 确定是什么机制控制了它们的表达。最初，一个 将进行描述性分析，以便仔细 描述这些基因的调控。随后，混合动力车 基因构建和缺失突变将用于 确定控制细胞周期和变体的序列元件 转录和翻译中的基因表达 级别。此外，H3基因内含子的功能 将被分析以确定对细胞周期的影响 对核加工和运输的控制和增加 H3.1基因内含子及H3.3基因内含子的缺失 吉恩。此外，高度的功能意义 保守的内含子区域，以及该基因的潜在功能作用 第一个内含子内的转录终止位点将是 进行了分析。

Histones are the major proteins in chromatin and act to package the DNA into nucleosomal structures. The recent characterization of a wide variety of variant and modified histones which are temporally and spatially regulated has implicated these proteins in control of gene expression during differentiation and aging. The ultimate purpose of this proposal is to determine the molecular mechanisms by which histone genes are so diversely regulated in order to approach questions regarding the function of these proteins. This will be accomplish by the detailed analysis the transcriptional, translational, and temporal regulation two members of the H3 subtype of histones. Particular attention will be paid to the detailed molecular structure of these genes and their mRNAs in an effort to determine what mechanisms control their expression. Initially, a descriptive analysis will be performed in order to carefully characterize the regulation of these genes. Subsequently, hybrid gene constructions and deletion mutations will be used to determine sequence elements that control cell cycle and variant gene expression at both the transcriptional and translational levels. Additionally, the function of the introns within H3 genes will be analysed to determine the consequences to cell cycle control and to nuclear processing and transport of the addition of introns to the H3.1 gene and the deletion of introns from the H3.3 gene. In addition, the functional significance of the highly conserved intronic region, and the potential functional role of the transcription termination site within the first intron will be analysed.