a quantitative model of transcriptional regulation reveals the influence of binding location on expression转录调控的定量模型揭示了绑定位置对表达的影响.pdfVIP

A Quantitative Model of Transcriptional Regulation Reveals the Influence of Binding Location on Expression 1 2 2 2 2 2,3 Kenzie D. MacIsaac , Kinyui A. Lo , William Gordon , Shmulik Motola , Tali Mazor , Ernest Fraenkel * 1 Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 2 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 3 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America Abstract Understanding the mechanistic basis of transcriptional regulation has been a central focus of molecular biology since its inception. New high-throughput chromatin immunoprecipitation experiments have revealed that most regulatory proteins bind thousands of sites in mammalian genomes. However, the functional significance of these binding sites remains unclear. We present a quantitative model of transcriptional regulation that suggests the contribution of each binding site to tissue-specific gene expression depends strongly on its position relative to the transcription start site. For three cell types, we show that, by considering binding position, it is possible to predict relative expression levels between cell types with an accuracy approaching the level of agreement between different experimental platforms. Our model suggests that, for the transcription factors profiled in these cell types, a regulatory site’s influence on expression falls off almost linearly with distance from the transc