Open AccessTranscription factor family‐specific DNA shape readout revealed by quantitative specificity models
Author(s) -
Yang Lin,
Orenstein Yaron,
Jolma Arttu,
Yin Yimeng,
Taipale Jussi,
Shamir Ron,
Rohs Remo
Publication year - 2017
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20167238
Subject(s) - dna , biology , computational biology , transcription factor , genetics , dna sequencing , systematic evolution of ligands by exponential enrichment , dna binding site , base pair , gene , promoter , rna , gene expression
Transcription factors ( TF s) 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 TF s. Overall, this work suggests a way of obtaining mechanistic insights into TF – DNA binding without relying on experimentally solved all‐atom structures.