Omics analysis of three-dimensional transcriptional regulation

三维转录调控的组学分析

• 批准号: 9418058
• 负责人: Victor Jin
• 金额: $ 32.52万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-13 至 2020-12-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9418058
• 关键词: Apoptosis; Architecture; Bayesian Modeling; Bioinformatics; Biological; Biological Assay; Biological Models; Breast Cancer Cell; Breast Cancer cell line; Cell Nucleus; Cell Proliferation; Chromatin; Communities; Complex; Computing Methodologies; Coupled; DNA Methylation; Data; Dimensions; EZH2 gene; Endocrine; Estrogen Receptor alpha; Estrogens; Euchromatin; Frequencies; Gene Expression Regulation; Gene Targeting; Genes; Genetic Transcription; Genomics; Goals; Heterochromatin; High-Throughput Nucleotide Sequencing; Histones; Hormones; Laboratories; Laws; Location; MCF7 cell; Maps; Measures; Mediating; Modeling; Molecular Conformation; Names; Nuclear; Oncogenic; Phenotype; Resistance; Resolution; Role; Statistical Models; Stimulus; Structure; Tamoxifen; Testing; Three-dimensional analysis; Time; Transcriptional Regulation; cell type; chromosome conformation capture; histone modification; malignant breast neoplasm; public health relevance; recruit; small hairpin RNA; three dimensional structure; three-dimensional modeling; tool; transcription factor

 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.

 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。我们提议的研究的成功完成将对基因组学界和一般生物学家具有价值，这可能会更好地理解3D转录调节的原理以及E2/ERa在内分泌耐药乳腺癌中的调节作用。