HISTONES IN CELL DIFFERENTIATION AND CARCINOGENESIS

细胞分化和癌变中的组蛋白

• 批准号: 3164096
• 负责人: ALFRED ZWEIDLER
• 金额: $ 18.92万
• 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 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3164096
• 关键词: animal age group; carcinogenesis; cell cycle; cell differentiation; cell growth regulation; chromatin; developmental genetics; electron microscopy; erythroleukemia; gel electrophoresis; gene expression; genetic regulation; genetic transcription; liver cells; liver regeneration; molecular oncology; mouse leukemia; mutant; neoplasm /cancer genetics; nucleosomes; peptidases; radiotracer; tissue /cell culture

We have identified a number of nonallelic histone variants which are involved both in the replication of chromosomes and in the maintenance and repair of tissue-specific patterns of chromatin conformation, an important mechanism for preserving the normal patterns of gene expression in long-lived, nondividing cells of adult mammals. We have identified several distinct modes of expression of histone gene clusters in the mouse genome using several histone variant mutants discovered by us. We have found the expression of different histone variants changes at the time of commitment of cells to terminal differentiation and that histone variant ratios are useful indicators of spontaneous or induced rates of cell turnover or regeneration in adult tissues. We are using histone variant ratios as an assay for studying commitment to terminal differentiation, a likely common defect in cancer cells, as well as for the development of a safe clinical test for chronically increased rates of cell turnover which may be an important cause of premature aging and tumor promotion. (D)

我们已经鉴定了许多非等位基因组蛋白变体，它们是 参与染色体的复制和维持 染色质构象的组织特异性模式的修复，一个重要的 维持基因表达正常模式的机制 成年哺乳动物的长寿、不分裂的细胞。 我们已经确定了几个 小鼠基因组中组蛋白基因簇的不同表达模式 使用我们发现的几种组蛋白变异突变体。 我们已经找到了 不同组蛋白变体的表达在承诺时发生变化 细胞至终末分化，组蛋白变异比例为 自发或诱导细胞更新率的有用指标或 成人组织的再生。 我们使用组蛋白变异比率作为 用于研究终末分化承诺的测定，这可能是常见的 癌细胞的缺陷，以及开发安全的临床 测试长期增加的细胞更新率，这可能是 早衰和肿瘤促进的重要原因。 (四)