FUNCTIONAL ANALYSIS OF THE SIR2 SILENCING PROTEIN

SIR2 沉默蛋白的功能分析

• 批准号: 6180819
• 负责人: LORRAINE PILLUS
• 金额: $ 23.69万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6180819
• 关键词: DNA binding protein; chimeric proteins; gene induction /repression; gene mutation; immunoelectron microscopy; immunofluorescence technique; posttranslational modifications; protein sequence; yeast two hybrid system

Successful transcriptional silencing of the majority of each eukaryotic genome is critical because inappropriate gene expression leads to disastrous consequences, including oncogenic transformation. The long-term goal of the proposed research is to understand fundamental mechanisms of transcriptional silencing. Discovery of homologs of the yeast silencing gene SIR2 from organisms as diverse as prokaryotes and mammals established an important new focus for studying silencing. Recent progress provides the first evidence for SIR-like silencing in humans and suggests that SIR2 silencing functions may be separated genetically. The primary goals of the research proposed are designed to address long-standing unanswered questions about SIR2 itself and specific questions and hypotheses raised in initial characterization of functionally conserved silencing domains. The project aims are to: .Extend biochemical and cell biological analyses of the SIR2 silencing protein. Pursue analysis of Sir2 protein domains identified for their significance in silencing and its specificity. Identify S1R2 interacting molecules in order to understand the mechanism of Sir2p's activity and regulation of its function. These aims will be accomplished through genetic, biochemical and cell biological approaches. Results obtained will lead to greater knowledge of silenced chromatin complexes and mechanisms of transcriptional control and genomic regulation conserved from yeast to humans. Progress made understanding these centrally important regulatory mechanisms may ultimately lead to improved diagnostics and refined therapeutic and genetic interventions for human diseases resulting from loss of gene regulation.

成功的转录沉默大多数的每一个 真核基因组是至关重要的，因为不适当的基因表达 导致灾难性的后果，包括致癌 转型拟议研究的长期目标是 理解转录沉默的基本机制。 酵母沉默基因SIR2同源物的发现 像原核生物和哺乳动物这样的生物， 研究沉默的重要新焦点。最新进展 提供了人类SIR样沉默的第一个证据， 表明SIR2沉默功能可能是分离的， 遗传的研究的主要目标是 旨在解决关于SIR2的长期未决问题 最初提出的具体问题和假设 功能上保守的沉默结构域的表征。的 项目的目标是：.扩展生物化学和细胞生物学 SIR2沉默蛋白的分析。Sir2的追踪分析 蛋白质结构域在沉默中的意义， 它的特异性。鉴定S1R2相互作用分子， 了解Sir2p的活性机制及其调控 功能这些目标将通过遗传、 生物化学和细胞生物学方法。取得的成果将 导致更多的沉默染色质复合物的知识， 转录控制和基因组调控机制 从酵母菌到人类都保存了下来在理解这些方面取得的进展 核心重要的监管机制可能最终导致 改善诊断和完善的治疗和遗传 基因缺失导致的人类疾病的干预措施 调控