A Technique for Measuring Transcription Factor Activity

摘要 几乎NIH的每个部门都在了解转录因子(TF)方面投入了大量资金。TF是 细胞的管理者，控制着从细胞类型到细胞反应再到压力的一切。与他们伟大的 难怪，许多人类疾病(癌症、家族性血小板紊乱、瓦登堡综合征、 等)由转录因子的突变所致。此外，超过75%的疾病变种在 人类基因组位于富含TF结合位点的调控区。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， 结合分析一次进行一个Tf。人们迫切需要的是一种能够 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，它利用增强子RNA来同时推断细胞中所有TF的活性。在这笔赠款中，我们 寻求优化我们的技术，使尔纳PROfiLING更准确、更快速、适用范围更广。

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.