The role of Topoisomerase II in insulator function

描述（由申请人提供）：高级染色质组织是真核基因表达的重要方面。吉普赛染色质绝缘子可能建立染色质结构域，这些结构域被认为通过控制细胞核内DNA的组织来调节基因表达。然而，这种染色质组织的建立和维持的机制还不清楚。我已经确定拓扑异构酶II作为一个潜在的调节绝缘子复合物和高阶染色质结构。该提案旨在更好地定义Topoll的这一角色，因为它与绝缘体功能有关。新的Topoll突变体的特点和基因测试与绝缘子功能的相互作用。此外，Topoll蛋白将检查其与体内绝缘子复合物的关联。最后，将采取生物化学方法，以更好地定义Topoll与绝缘子DNA和蛋白质的相互作用。通过这些研究，我希望更好地定义Topoll与绝缘子功能和高级染色质组织的联系。

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.