HISTONES IN CELL DIFFERENTIATION & CARCINOGENESIS

细胞分化中的组蛋白

• 批准号: 3164097
• 负责人: ALFRED ZWEIDLER
• 金额: $ 17.84万
• 依托单位: FOX CHASE CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-04-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3164097
• 关键词: DNA binding protein; DNA footprinting; animal age group; binding proteins; carcinogenesis; cell cycle; cell differentiation; cell growth regulation; chemical binding; chromatin; conformation; electron microscopy; gel electrophoresis; gene expression; genetic manipulation; genetic regulation; genetic transcription; histones; laboratory mouse; liver cells; molecular oncology; mutant; neoplasm /cancer genetics; nucleosomes; protein structure function; radiotracer; tissue /cell culture

Our long range goal is the elucidation of the molecular mechanisms responsible for the differential expression of genes in specialized mammalian cells, as a basis for better understanding and treatment of human health problems caused by defects in cell differentiation, including aging and cancer. The tissue-specific pattern of gene expression is reflected in a corresponding pattern of different chromatin conformation. The primary determinants of chromatin conformation are the histones. We have described a number of nonallelic primary structure variants of mammalian histones which are expressed under different circumstances and occur in different proportions in adult tissues. In order to elucidate the specific functions of each histone species and its variants, we are defining on the molecular level the properties and dynamics of specific protein-protein and protein-DNA interactions which are responsible for different aspects of nucleosome architecture and chromatin conformation. For this purpose we have developed protein "footprinting" assays which measure simultaneously the degree of protection of a large number of specific sites in the presumptive binding domains of the core histones. These assays will be used to compare nucleosomes containing different variants as well as chromatin in different functional states.

我们的长期目标是阐明 基因差异表达的机制， 专门的哺乳动物细胞，作为更好地理解 和治疗由细胞缺陷引起的人类健康问题 分化，包括衰老和癌症。 组织特异 基因表达的模式反映在相应的模式中 不同的染色质构象。 主要决定因素 是组蛋白。 我们已经描述了 哺乳动物的非等位基因一级结构变体的数量 在不同情况下表达的组蛋白， 在成人组织中以不同比例存在。 为了 阐明每个组蛋白种类的具体功能及其 变体，我们在分子水平上定义了 以及特定蛋白质-蛋白质和蛋白质-DNA的动力学 这些相互作用负责不同方面的 核小体结构和染色质构象。 为此 我们已经开发了蛋白质“足迹”测定法， 同时衡量保护程度的一个大 的假定结合结构域中的特定位点的数目。 核心组蛋白 这些分析将用于比较核小体 包含不同的变体以及不同的染色质 功能状态。