Dissecting RNAi-mediated Heterochromatin Formation

剖析 RNAi 介导的异染色质形成

• 批准号: 7107277
• 负责人: RICHARD J LAWRENCE
• 金额: $ 4.88万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7107277
• 关键词: RNA interference; Schizosaccharomyces pombe; biotechnology; centromere; chromatin immunoprecipitation; double stranded RNA; fungal genetics; gene induction /repression; genetic screening; genetic transcription; heterochromatin; molecular genetics; molecular site; postdoctoral investigator

DESCRIPTION (provided by applicant): Heterochromatin was originally defined as loci of nuclear DNA that remain highly condensed during interphase. Faithful chromosome segregation and genome stability requires heterochromatin, demonstrating the critical importance of assembling these loci; in fact, knockout mice for Suv39h, a component required for heterochromatin formation, have increased tumor risks. Recent data indicates that the RNAi machinery is required for heterochromatization by an as yet unknown mechanism. We have designed experiments that will address this problem in the genetically tractable fission yeast, S. pombe. We intend to determine (1) whether RNAi mediates heterochromatin formation in cis or in trans or both, (2) whether heterochromatin targeting requires transcription of the target locus, (3) whether RNAi-mediated heterochromatin formation is heritable in the absence of dsRNA, (4) whether RNAi-mediated heterochromatin formation results in heterochromatin spreading, and (5) the order of assembly of components of the RNAi and heterochromatin-specifying machinery. Furthermore, we have designed a novel genetic screen to isolate novel factors that are both required for and disrupt RNAi-mediated heterochromatin formation.

描述(申请人提供)：异染色质最初被定义为在间期保持高度浓缩的核DNA的基因座。忠实的染色体分离和基因组稳定性需要异染色质，这证明了组装这些基因座的关键重要性；事实上，Suv39h基因敲除小鼠--异染色质形成所需的一个组成部分--增加了肿瘤风险。最近的数据表明，RNAi机制是异染色化所必需的，机制尚不清楚。我们设计的实验将在基因易驯化的分裂酵母S.pombe中解决这个问题。我们打算确定(1)RNAi是否在顺式或反式或两者中介导异染色质的形成，(2)异染色质靶向是否需要靶基因的转录，(3)RNAi介导的异染色质形成在没有dsRNA的情况下是否可遗传，(4)RNAi介导的异染色质形成是否导致异染色质的扩散，以及(5)RNAi和异染色质指定机制的组件的组装顺序。此外，我们设计了一种新的遗传筛选来分离RNAi介导的异染色质形成所需和破坏的新因子。

项目成果

Msc1 links dynamic Swi6/HP1 binding to cell fate determination.

Msc1 将动态 Swi6/HP1 结合与细胞命运决定联系起来。

• DOI: 10.1073/pnas.0811161106
• 发表时间: 2009
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Lawrence,RichardJ;Volpe,ThomasA
• 通讯作者: Volpe,ThomasA