Transcription factor family-specific DNA shape readout revealed by quantitative specificity models

Lin Yang, Yaron Orenstein, Arttu Jolma, Yimeng Yin, Jussi Taipale, Ron Shamir, Remo Rohs

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

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.

Original languageEnglish
Article number910
JournalMolecular Systems Biology
Volume13
Issue number2
DOIs
StatePublished - 1 Feb 2017
Externally publishedYes

Keywords

  • DNA shape
  • binding specificity
  • feature selection
  • quantitative modeling
  • transcription factor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Immunology and Microbiology (all)
  • Agricultural and Biological Sciences (all)
  • Applied Mathematics

Fingerprint

Dive into the research topics of 'Transcription factor family-specific DNA shape readout revealed by quantitative specificity models'. Together they form a unique fingerprint.

Cite this