Proteins and Enzymes Affecting Chromatin

长期的目标是了解真核细胞核，使用酵母，酿酒酵母，作为一个模型系统。其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的异染色质。Sir 3和Sir 4蛋白在沉默中的作用将被详细研究。具体而言，Sir 3 N-末端BAH结构域和Sir 4的保守结构域的作用将被研究。乙酰ADP-核糖作为沉默的信号分子的可能作用将被检查。还将研究Sir 4的可能的sumoylation。 另一个目标是寻找组蛋白去甲基化酶基因。最近的研究表明，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，但没有赖氨酸脱甲基酶基因或酶已被确定。将采取各种生物化学和遗传学方法来寻找这样的基因。在这些领域的进展将揭示染色体结构和功能的真核细胞核，不仅在酵母，而且在哺乳动物细胞。

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.