A Technique for Measuring Transcription Factor Activity

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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 using the location of all eRNAs. The primary goal of this diversity supplement extension request is to evaluate in vivo the limits of our computational modeling towards predicting the activity of TFs. In this way, we seek to optimize our technology, making eRNA profiling more accurate, fast and broadly applicable.