Final Report Summary - TRANSCRIPTION_REG (A combined experimental and computational approach for quantitative and mechanistic understanding of transcriptional regulation)
Transcriptional regulation is the process by which cells control the times and locations at which to activate their various genes. It plays a central role in nearly all biological activities, including development and differentiation, and many human diseases are caused by defects in this process. For these reasons, much effort was devoted to studying transcriptional regulation, and tremendous progress, using a wide range of genetic, molecular, and biochemical techniques, has been made in identifying the transcription factors, regulatory DNA elements, and other building blocks involved in regulating transcription in several specific systems. However, very few concerted attempts have been made at going beyond qualitative descriptions. Consequently, we are still far from a quantitative and predictive understanding of transcriptional control.
The long-term goal of this ERC project was to develop a mechanistic understanding of transcriptional regulation, and arrive at a model for the entire process, from the expression of the transcription factors to their binding to cis-regulatory sequence, through the role of chromatin in this process, and up to the expression patterns that result from these binding events. Notably, we went much beyond identifying and qualitatively describing the components involved, and derived a quantitative understanding of how transcriptional programs are encoded in DNA sequence. We believe that the advances that we made in this problem may have far reaching implications, e.g. for understanding the expression and phenotypic variation that is caused by genetic variation among human individuals, and one of the final works that we devised in this project demonstrated the ability to predict expression level differences among human individuals using only their genotype information.
The long-term goal of this ERC project was to develop a mechanistic understanding of transcriptional regulation, and arrive at a model for the entire process, from the expression of the transcription factors to their binding to cis-regulatory sequence, through the role of chromatin in this process, and up to the expression patterns that result from these binding events. Notably, we went much beyond identifying and qualitatively describing the components involved, and derived a quantitative understanding of how transcriptional programs are encoded in DNA sequence. We believe that the advances that we made in this problem may have far reaching implications, e.g. for understanding the expression and phenotypic variation that is caused by genetic variation among human individuals, and one of the final works that we devised in this project demonstrated the ability to predict expression level differences among human individuals using only their genotype information.