title: Protein-DNA binding in the absence of specific base-pair recognition.
abstract: 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 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.
authors.affiliation: Department of Chemistry, Ben-Gurion University of the Negev, Be'er Sheva 8410501 Israel; and.
authors.forename: Ariel
authors.initials: A
authors.lastname: Afek
authors.affiliation: Center for Genomic and Computational Biology, Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27708.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Schipper
authors.affiliation: Center for Genomic and Computational Biology, Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27708.
authors.forename: John
authors.initials: J
authors.lastname: Horton
authors.affiliation: Center for Genomic and Computational Biology, Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27708 lukatsky@bgu.ac.il raluca.gordan@duke.edu.
authors.forename: Raluca
authors.initials: R
authors.lastname: Gordân
authors.affiliation: Department of Chemistry, Ben-Gurion University of the Negev, Be'er Sheva 8410501 Israel; and lukatsky@bgu.ac.il raluca.gordan@duke.edu.
authors.forename: David B
authors.initials: DB
authors.lastname: Lukatsky
mesh_terms: D000465:Algorithms; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013816:Thermodynamics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004247:DNA
keywords: nonspecific protein−DNA binding; protein−DNA binding; transcriptional regulation