Omics analysis of three-dimensional transcriptional regulation

 描述（由申请人提供）：在该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）TF模块形成不同的转录染色质枢纽并共同调节动态相互作用组;以及2）环境或细胞刺激（如激素）触发不同的转录调节剂以促进动态染色质构象变化。最终目标是从一维到三维的尺度上对TF模块进行建模和分析，并描述染色质组织与TF模块之间的关系。使用乳腺癌中ER α的模型系统，我们的研究将检查1）E2介导的动态TF转录模块和染色质相互作用;和2）这些枢纽和相互作用结构域在他莫昔芬耐药乳腺癌细胞中被改变。我们提出的研究的成功完成将是有价值的基因组学社区和生物学家一般，这可能会导致更好地理解的三维转录调控的原则和E2/ERa的内分泌耐药乳腺癌的调节作用。

 DESCRIPTION (provided by applicant): In this R01 proposal, we plan to use an integrative genomics (Omics) analysis to test two central hypotheses: 1) TF modules form different transcriptional chromatin hubs and co-regulate dynamical interactomes; and 2) an environmental or cellular stimulus such as hormones triggers different transcription modulators to facilitate dynamical chromatin conformation changes. The ultimate goal is to model and analyze TF modules from one- dimension (1D) to three-dimension (3D) scale and describe the relationship between chromatin organization and TF modules. Using a model system of ERa in breast cancer, our studies will examine 1) E2-mediated dynamic TF transcription modules and chromatin interactions; and 2) these hubs and interacting domains are altered in tamoxifen resistant breast cancer cells. 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 principle of 3D transcriptional regulation and the regulatory role of E2/ERa in endocrine resistant breast cancer.