Transcription factor family‐specific DNA shape readout revealed by quantitative specificity models
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Author(s)
Yang, Lin
Orenstein, Yaron
Jolma, Arttu
Yin, Yimeng
Taipale, Jussi
Shamir, Ron
Rohs, Remo
Date Issued
February 2017
Journal
Molecular Systems Biology
Publisher
Nature Publishing Group
Citation
Yang, Lin et al. “Transcription Factor Family‐specific DNA Shape Readout Revealed by Quantitative Specificity Models.” Molecular Systems Biology 13, 2 (February 2017): 910 © 2017 The Authors
Version
Final published version
Abstract
Transcription factors (TFs) achieve DNA-binding specificity through contacts with functional groups of bases (base readout) and readout of structural properties of the double helix (shape readout). Currently, it remains unclear whether DNA shape readout is utilized by only a few selected TF families, or whether this mechanism is used extensively by most TF families. We resequenced data from previously published HT-SELEX experiments, the most extensive mammalian TF–DNA binding data available to date. Using these data, we demonstrated the contributions of DNA shape readout across diverse TF families and its importance in core motif-flanking regions. Statistical machine-learning models combined with feature-selection techniques helped to reveal the nucleotide position-dependent DNA shape readout in TF-binding sites and the TF family-specific position dependence. Based on these results, we proposed novel DNA shape logos to visualize the DNA shape preferences of TFs. Overall, this work suggests a way of obtaining mechanistic insights into TF–DNA binding without relying on experimentally solved all-atom structures.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.15252/msb.20167238
