Omics analysis of three-dimensional transcriptional regulation

摘要 在这个R 01提案中，我们计划使用整合基因组学（组学）分析来测试两个中心假设： 1)环境或细胞刺激如激素诱导不同的染色质相互作用灶， 增强子-增强子环化灶在调节细胞转化表型中起关键作用;和2）3D染色质 结构在控制细胞身份方面起着关键作用。最终目的是剖析 染色质相互作用和细胞身份或细胞表型。乳腺ERα模型系统的建立 癌症，我们将a）确定不同类型的ERα调节的染色质相互作用灶，包括启动子- 增强子、增强子-增强子和增强子-阻遏子成环灶;和B）鉴定3D调节的乳腺癌 细胞特性和敏感-抗性过渡细胞亚群。成功完成我们的建议 研究将对基因组学社区和一般生物学家有价值，这可能会导致更好的 理解增强子-增强子相互作用网络对各种功能的贡献， 生物过程，特别是乳腺癌内分泌抵抗，以及3D染色质结构如何 将乳腺癌敏感细胞亚群控制为耐药细胞亚群。

Abstract In this R01 proposal, we plan to use an integrative genomics (Omics) analysis to test two central hypotheses: 1) an environmental or cellular stimulus such as hormones induced distinct chromatin interacting foci such as enhancer-enhancer looping foci play key roles in regulating cell transformed phenotype; and 2) 3D chromatin structures play key roles in governing cell identities. The ultimate goal is to dissect the relationship between chromatin interactions and cell identities or cellular phenotypes. Using a model system of ERα in breast cancer, we will a) identify distinct types of ERα-regulated chromatin interacting foci including promoter- enhancer, enhancer-enhancer and enhancer-repressor looping foci; and b) identify 3D-regulated breast cancer cell identities and sensitive-resistant transition cell subpopulations. The successful completion of our proposed studies will be of value to the genomics community and biologists in general, which may result in the better understanding of the contribution of enhancer-enhancer interacting network towards functions of various biological processes, in particular breast cancer endocrine resistance, and on how 3D chromatin structure governs the breast cancer sensitive cell subpopulations into resistant cell subpopulations.