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Omics analysis of three-dimensional transcriptional regulation

三维转录调控的组学分析

基本信息

批准号：
10656631
负责人：
Victor Jin
金额：
$ 28.81万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-13 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10656631
关键词：
3-Dimensional Address Apoptosis Architecture Awareness Bayesian Method Biological Assay Biological Models Biological Process Breast Cancer Cell CRISPR/Cas technology Cell Line Cell Nucleus Cell Proliferation Cell model Cells Characteristics Chromatin Chromatin Loop Chromatin Structure Chromosome Territory Communities Complex Computer Analysis Computer Models Computing Methodologies Data Data Set Dropout Endocrine Enhancers Epigenetic Process Estrogen Receptor alpha Estrogens Funding Gene Expression Regulation Genes Genomics Goals Graph HDAC3 gene Hi-C Higher Order Chromatin Structure Hormones Human Genome KDM1A gene Lead MCF7 cell Malignant Neoplasms Measures Metabolism Methods Modeling Modification Names Outcome Measure Phenotype Play Resistance Signal Pathway Statistical Methods Stimulus T47D Tamoxifen Technology Testing Three-dimensional analysis Time Transcriptional Regulation Transitional Cell cancer cell cell transformation cell type experimental study gain of function malignant breast neoplasm malignant endocrine gland neoplasm novel preservation prognostic signature promoter

项目摘要

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.

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。