The role of Topoisomerase II in insulator function

描述(申请人提供)：高阶染色质组织是真核基因表达的一个重要方面。吉普赛人染色质绝缘体可以建立染色质结构域，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，管理这个染色质组织的建立和维持的机制还不是很清楚。我已经确定拓扑异构酶II是绝缘体复合体和高阶染色质结构的潜在调节因子。该提案旨在更好地定义Topoll的这一角色，因为它与绝缘子功能有关。将对新的Topoll突变体进行表征，并对其与绝缘子功能的相互作用进行遗传测试。此外，还将在体内检查Topoll蛋白与绝缘体复合体的联系。最后，将采用生化方法更好地定义Topoll与绝缘体DNA和蛋白质的相互作用。通过这些研究，我希望更好地确定Topoll与绝缘体功能和高阶染色质组织的联系。

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.