title: A deeper look into transcription regulatory code by preferred pair distance templates for transcription factor binding sites.
abstract: BACKGROUND
  Modern experimental methods provide substantial information on protein-DNA recognition. Studying arrangements of transcription factor binding sites (TFBSs) of interacting transcription factors (TFs) advances understanding of the transcription regulatory code.
  
  
  RESULTS
  We constructed binding motifs for TFs forming a complex with HIF-1α at the erythropoietin 3(')-enhancer. Corresponding TFBSs were predicted in the segments around transcription start sites (TSSs) of all human genes. Using the genome-wide set of regulatory regions, we observed several strongly preferred distances between hypoxia-responsive element (HRE) and binding sites of a particular cofactor protein. The set of preferred distances was called as a preferred pair distance template (PPDT). PPDT dramatically depended on the TF and orientation of its binding sites relative to HRE. PPDT evaluated from the genome-wide set of regulatory sequences was used to detect significant PPDT-consistent binding site pairs in regulatory regions of hypoxia-responsive genes. We believe PPDT can help to reveal the layout of eukaryotic regulatory segments.
  
  
  BACKGROUND
  ivan.kulakovskiy@gmail.com
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Laboratory of Bioinformatics and System Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia. ivan.kulakovskiy@gmail.com
authors.forename: I V
authors.initials: IV
authors.lastname: Kulakovskiy
authors.forename: A A
authors.initials: AA
authors.lastname: Belostotsky
authors.forename: A S
authors.initials: AS
authors.lastname: Kasianov
authors.forename: N G
authors.initials: NG
authors.lastname: Esipova
authors.forename: Y A
authors.initials: YA
authors.lastname: Medvedeva
authors.forename: I A
authors.initials: IA
authors.lastname: Eliseeva
authors.forename: V J
authors.initials: VJ
authors.lastname: Makeev
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D001665:Binding Sites / Q000235:genetics*; D004247:DNA / Q000378:metabolism*; D004921:Erythropoietin / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D016678:Genome; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D059372:Nucleotide Motifs; D011485:Protein Binding / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011506:Proteins; D014157:Transcription Factors; D004921:Erythropoietin; D004247:DNA