Role of Topoisomerase II in insulator function

拓扑异构酶 II 在绝缘体功能中的作用

• 批准号: 6999996
• 负责人: Edward Ramos
• 金额: $ 4.83万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999996
• 关键词: DNA topoisomerases; cell biology; chromatin; enzyme activity; gene expression; gene mutation; genetic manipulation; genetic regulatory element; laboratory rabbit; laboratory rat; postdoctoral investigator; protein localization; protein protein interaction; protein structure function

DESCRIPTION (provided by applicant): Higher-order chromatin organization is an essential aspect for the expression of eukaryotic genes. The gypsy chromatin insulator may establish chromatin domains that are thought to regulate gene expression by controlling the organization of DNA within the nucleus. However, the mechanism governing the establishment and maintenance of this chromatin organization is not well understood. I have identified Topoisomerase II as a potential regulator of insulator complexes and higher-order chromatin structure. This proposal seeks to better define this role for Topoll as it relates to insulator function. Novel Topoll mutants will be characterized and genetically tested for their interaction with insulator function. In addition, the Topoll protein will be examined for its association with insulator complexes in vivo. Finally, a biochemical approach will be undertaken to better define Topoll interaction with insulator DNA and proteins. From these studies I hope to better define the connection of Topoll as it pertains to insulator function and higher-order chromatin organization.

描述（由申请人提供）：高阶染色质组织是表达真核基因的重要方面。吉普赛染色质绝缘子可以建立染色质结构域，这些染色质结构被认为可以通过控制核内的DNA的组织来调节基因表达。但是，对该染色质组织的建立和维护的机制尚不清楚。我已经将拓扑异构酶II确定为绝缘子复合物和高阶染色质结构的潜在调节剂。该建议旨在更好地定义与绝缘体功能有关的Topoll的角色。新型的托托尔突变体将被表征并在遗传测试中与绝缘函数的相互作用进行遗传测试。此外，将检查托托蛋白与体内绝缘子复合物的关联。最后，将采用生化方法来更好地定义与绝缘子DNA和蛋白质的相互作用。从这些研究中，我希望更好地定义Topoll与绝缘体功能和高阶染色质组织的联系。