A Technique for Measuring Transcription Factor Activity

测量转录因子活性的技术

• 批准号: 10204040
• 负责人: Robin DeAnne Dowell-Deen
• 金额: $ 28.76万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-05 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10204040
• 关键词: Algorithms; Antibodies; Behavior; Binding; Binding Sites; Biological Assay; Cells; Chromatin; DNA; Data Set; Disease; Drug Screening; ESR1 gene; Engineering; Enhancers; Estradiol; Familial Platelet Disorder; Genes; Genetic Transcription; Goals; Grant; Human; Human Genome; Location; Malignant Neoplasms; Measures; Methods; Modeling; Mutation; Nucleic Acid Regulatory Sequences; Pattern; Polymerase; Post-Translational Protein Processing; Protein Isoforms; Proteins; Publishing; RNA; Regulation; Reporter; Research; Site; Stimulus; Stress; Techniques; Technology; Time; United States National Institutes of Health; Variant; Waardenburg syndrome; Work; cell type; chromatin immunoprecipitation; cooking; disease-causing mutation; experience; experimental study; genome-wide; human disease; improved; machine learning algorithm; novel; novel strategies; prototype; response; transcription factor

Summary Almost every division of NIH has invested heavily in understanding transcription factors (TFs). TFs are the managers of the cell, controlling everything from cell type to cellular response to stress. With their great power, it is no wonder, many human disorders (cancer, familial platelet disorder, Waardenburg syndrome, etc.) result from mutations in transcription factors. Moreover, over 75% of disease causing variants within the human genome reside in regulatory regions, which are dense with TF binding sites. Currently we can measure the location of TF binding, but binding does not equate with regulatory activity. Furthermore, binding analysis is conducted one TF at a time. What is desperately needed is a technology that is able to measure the activity of all TFs in a cell simultaneously. We have developed a novel approach, called eRNA profiling, that leverages enhancer RNAs to infer the activity of all TFs in a cell simultaneously. In this grant we seek to optimize our technology, making eRNA profiling more accurate, fast and broadly applicable.

总结 几乎NIH的每个部门都投入了大量资金来了解转录因子（TF）。TF是 细胞的管理者，控制着从细胞类型到细胞对压力的反应的一切。他们伟大的 权力，这是不足为奇的，许多人类疾病（癌症，家族性血小板疾病，Waardenburg综合征， 等等）。是由转录因子的突变引起的。此外，超过75%的致病变异在 人类基因组存在于调节区，其密集有TF结合位点。目前我们可以 测量TF结合的位置，但结合并不等同于调节活性。此外，委员会认为， 每次进行一个TF的结合分析。我们迫切需要的是一种技术， 同时测量细胞中所有TF的活性。我们开发了一种新的方法，称为eRNA profiling，利用增强子RNA同时推断细胞中所有TF的活性。在这份协议中，我们 寻求优化我们的技术，使eRNA分析更准确，更快速，更广泛地适用。