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连接子组蛋白的功能及其相关性 它们的多样性。H1组蛋白被认为有助于折叠 染色质进入高阶结构，从而影响基因表达 以及其他需要获取DNA的过程。大多数关于这方面的知识 H1组蛋白的功能来源于体外研究。 这项建议将分析H1组蛋白在小鼠体内的功能。 小鼠和其他哺乳动物至少有7种不同的H1组蛋白亚型 它们在初级序列和表达上有很大的差异 发展。在这项提案中要检验的工作假设是 不同的H1亚型有助于在体内建立差异 染色质结构和基因调控的差异。中国的战略 研究特定H1亚型的功能是生成和 描述一个或多个H1基因被敲除的小鼠的特征。基因 将使用停用来1)确定消除一个H1的效果 亚型对特定组织表型和基因表达模式的影响 2)确定消除几种H1亚型的效果 以便同时产生其中几个组织包含 主要是一个亚型，甚至是总连接物组蛋白的很大缺陷 内容。H1组蛋白参与调控的机制 转录将通过比较 特定基因的附近。该提案还将描述一种新的、 潜在的新的H1基因，并试图识别其他与H1相关的基因 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.