Omics analysis of three-dimensional transcriptional regulation

摘要 在这份R01提案中，我们计划使用综合基因组学(OMICS)分析来测试两个中心假设： 1)环境或细胞刺激，如激素引起的不同染色质相互作用的焦点，如 增强子-增强子环状区在调节细胞转化表型中起关键作用；2)3D染色质 结构在管理细胞身份方面发挥着关键作用。最终的目标是剖析两者之间的关系 染色质相互作用和细胞特性或细胞表型。ER-α模型系统在乳腺中的应用 癌症，我们将a)确定不同类型的ERα调节的染色质相互作用的焦点，包括启动子- 增强子、增强子-增强子和增强子-抑制子环状焦点；以及b)识别3D调控的乳腺癌 细胞特性和耐药过渡细胞亚群。圆满完成我们提议的 研究将对基因组学社区和整个生物学家有价值，这可能会带来更好的结果 理解增强子-增强子相互作用网络对多种功能的贡献 生物学过程，特别是乳腺癌内分泌耐药，以及3D染色质是如何结构的 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.