Protein-DNA binding in the absence of specific base-pair recognition

Ariel Afek, Joshua L. Schipper, John Horton, Raluca Gordân, David B. Lukatsky

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Until now, it has been reasonably assumed that specific base-pair recognition is the only mechanism controlling the specificity of transcription factor (TF)-DNA binding. Contrary to this assumption, here we show that nonspecific DNA sequences possessing certain repeat symmetries, when present outside of specific TF binding sites (TFBSs), statistically control TF -DNA binding preferences. We used highthroughput protein-DNAbinding assays to measure the binding levels and free energies of binding for several humanTFs to tens of thousands of short DNA sequences with varying repeat symmetries. Based on statisticalmechanicsmodeling, weidentifyanewprotein-DNAbinding mechanism induced by DNA sequence symmetry in the absence of specific base-pair recognition, and experimentally demonstrate that this mechanism indeed governs protein-DNA binding preferences.

Original languageEnglish
Pages (from-to)17140-17145
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number48
StatePublished - 2 Dec 2014


  • Nonspecific protein-DNA binding
  • Protein-DNA binding
  • Transcriptional regulation

ASJC Scopus subject areas

  • General


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