IN VIVO ANALYSIS OF MOUSE H1 HISTONE FUNCTION

描述：拟议研究的目标是推进我们的 理解H1连接组蛋白的功能及其与 他们的多样性。 H1组蛋白被认为有助于 染色质进入更高级的结构，从而影响基因表达 和其他需要DNA的过程。 大部分关于 H1组蛋白的功能来自体外研究。 本研究将在小鼠体内分析H1组蛋白的功能。 小鼠和其他哺乳动物至少有7种不同的H1组蛋白亚型 它们的一级序列和表达在 发展 本提案中有待检验的工作假设是， 不同的H1亚型有助于建立体内差异 染色质结构和基因调控的差异。 战略 研究特定H1亚型的功能是产生和 表征其中一个或多个H1基因已被敲除的小鼠。 基因 灭活将用于1）确定消除一个H1的效果 表型和特定组织中基因表达模式的亚型 和2）确定消除几种H1亚型的效果 从而产生其中几种组织包含 大多数是一种亚型，甚至是整个连接组蛋白的大量缺乏 内容 H1组蛋白参与调控的机制 转录将通过比较染色质结构进行分析， 特定基因附近。 该提案还将提出一个新的， 潜在的新的H1基因，并试图确定其他H1相关基因， 老鼠的基因组

DESCRIPTION: The goals of the proposed research are to advance our understanding of the functions of the H1 linker histones and the relevance of their diversity. H1 histones are thought to facilitate the folding of chromatin into higher order structures and thereby influence gene expression and other processes requiring access to DNA. Most of the knowledge about the functions of the H1 histones has been derived from in vitro studies. This proposal will analyze the functions of H1 histones in vivo in mice. Mice and other mammals have at least 7 different subtypes of H1 histones that differ considerably in their primary sequence and expression during development. The working hypothesis to be tested in this proposal is that different H1 subtypes contribute to establishing differences in vivo chromatin structures and differences in gene regulation. The strategy for studying the function of specific H1 subtypes is to generate and characterize mice in which one or more H1 genes have been knocked out. Gene inactivation will be used to 1) determine the effect of eliminating one H1 subtype on the phenotype and on gene expression patterns in specific tissue and 2) to determine the effect of eliminating several H1 subtypes simultaneously so as to generate animals in which several tissues contain mostly one subtype or even a large deficiency in total linker histone content. The mechanisms by which H1 histones participate in regulating transcription will be analyzed by comparing the chromatin structure in the vicinity of specific genes. The proposal will also characterize a new, potentially novel H1 gene and attempt to identify other H1-related genes in the mouse genome.