RT Journal Article SR Electronic T1 Mapping DNA sequence to transcription factor binding energy in vivo JF bioRxiv FD Cold Spring Harbor Laboratory SP 331124 DO 10.1101/331124 A1 Stephanie L. Barnes A1 Nathan M. Belliveau A1 William T. Ireland A1 Justin B. Kinney A1 Rob Phillips YR 2018 UL http://biorxiv.org/content/early/2018/05/25/331124.abstract AB Despite the central importance of transcriptional regulation in systems biology, it has proven difficult to determine the regulatory mechanisms of individual genes, let alone entire gene networks. It is particularly difficult to analyze a promoter sequence and identify the locations, regulatory roles, and energetic properties of binding sites for transcription factors and RNA polymerase. In this work, we present a strategy for interpreting transcriptional regulatory sequences using in vivo methods (i.e. the massively parallel reporter assay Sort-Seq) to formulate quantitative models that map a transcription factor binding site’s DNA sequence to transcription factor-DNA binding energy. We use these models to predict the binding energies of transcription factor binding sites to within 1 kBT of their measured values. We further explore how such a sequence-energy mapping relates to the mechanisms of trancriptional regulation in various promoter contexts. Specifically, we show that our models can be used to design specific induction responses, analyze the effects of amino acid mutations on DNA sequence preference, and determine how regulatory context affects a transcription factor’s sequence specificity.