Proteins and Enzymes Affecting Chromatin

影响染色质的蛋白质和酶

• 批准号: 6905609
• 负责人: Rolf Sternglanz
• 金额: $ 36.87万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6905609
• 关键词: DNA replication; Saccharomyces cerevisiae; chromatin; chromosomes; enzyme mechanism; fungal genetics; gene expression; genetic transcription; high performance liquid chromatography; histones; nucleoproteins; protein structure function; telomere; yeast two hybrid system

The long term objective is to understand the eukaryotic nucleus, using the yeast, Saccharomyces cerevisiae, as a model system. The goal is to identify and characterize genes affecting the structure and function of chromosomes. Current effort is focused on understanding the mechanism of transcriptional silencing of the yeast silent mating-type loci and telomeres. These silenced chromosomal domains are the yeast equivalent of heterochromatin in metazoans. The roles of Sir3 and Sir4 proteins in silencing will be studied in detail. Specifically, the role of the Sir3 N-terminal BAH domain and a conserved domain of Sir4 will be investigated. The possible role of acetyl ADP-ribose as a signalling molecule in silencing will be examined. The possible sumoylation of Sir4 will also be studied. Another aim will be to search for a histone demethylase gene. Recent work has shown that methylation of specific lysine residues of histones H3 and H4 is very important for gene regulation. There is some evidence that this modification is reversible but no lysine demethylase gene or enzyme has been identified. Various biochemical and genetic approaches will be undertaken to find such a gene. Progress in these areas will shed light on chromosome structure and function in the eukaryotic nucleus, not only in yeast but also in mammalian cells.

长期目标是使用酿酒酵母作为模型系统来了解真核细胞核。目标是识别和表征影响染色体结构和功能的基因。目前的工作重点是了解酵母沉默交配型基因座和端粒的转录沉默机制。这些沉默的染色体结构域相当于后生动物中异染色质的酵母。我们将详细研究 Sir3 和 Sir4 蛋白在沉默中的作用。具体来说，将研究 Sir3 N 端 BAH 结构域和 Sir4 保守结构域的作用。将检查乙酰 ADP-核糖作为信号分子在沉默中的可能作用。 Sir4 可能的 sumoylation 也将被研究。 另一个目标是寻找组蛋白去甲基化酶基因。最近的工作表明，组蛋白 H3 和 H4 的特定赖氨酸残基的甲基化对于基因调控非常重要。有一些证据表明这种修饰是可逆的，但尚未鉴定出赖氨酸脱甲基酶基因或酶。将采取各种生化和遗传学方法来寻找这样的基因。这些领域的进展将揭示真核细胞核中的染色体结构和功能，不仅在酵母中，而且在哺乳动物细胞中。