Protein-DNA Binding in the Absence of Specific Base-Pair Recognition

David Lukatsky, Chemistry, Ben Gurion University of the Negev, Beer-Sheva, Israel

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, we have shown 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 high-throughput protein-DNA binding assays to measure the binding levels and free energies of binding for several human TFs to tens of thousands of short DNA sequences with varying repeat symmetries. Based on statistical mechanics modeling, we identify a new protein-DNA binding 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.

References: Ariel Afek, Joshua L. Schipper, John Horton, Raluca Gordân, and David B. Lukatsky, Proc. Natl. Acad. Sci. USA, doi: 10.1073/pnas.1410569111, (Early Edition, Oct 13) (2014) http://www.pnas.org/content/early/2014/10/08/1410569111.abstract