A deeper look into transcription regulatory code by preferred pair distance templates for transcription factor binding sites

Bioinformatics. 2011 Oct 1;27(19):2621-4. doi: 10.1093/bioinformatics/btr453. Epub 2011 Aug 18.

Abstract

Motivation: 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.

Contact: ivan.kulakovskiy@gmail.com

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / genetics
  • Binding Sites / genetics*
  • DNA / metabolism*
  • Erythropoietin / genetics
  • Gene Expression Regulation / genetics*
  • Genome
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Nucleotide Motifs
  • Protein Binding / genetics
  • Proteins / genetics
  • Proteins / metabolism
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Initiation Site

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Proteins
  • Transcription Factors
  • Erythropoietin
  • DNA