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Phylogeny based discovery of regulatory elements.

Jason Gertz1, Justin C Fay, Barak A Cohen

  • 1Department of Genetics, Washington University School of Medicine, 4444 Forest Park Parkway, St. Louis, MO 63108, USA. jgertz@genetics.wustl.edu

BMC Bioinformatics
|May 24, 2006
PubMed
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This study introduces a new computational framework for identifying functional DNA elements by modeling constrained DNA sequence evolution. The method successfully predicted novel regulatory motifs, including one experimentally validated element involved in glucose response.

Area of Science:

  • Computational Biology
  • Genomics
  • Bioinformatics

Background:

  • Evolutionarily conserved sequences aid in finding functional DNA elements like transcription factor binding sites.
  • Existing methods often lack explicit models for the constrained evolution of functional DNA sequences.

Purpose of the Study:

  • To develop a probabilistic framework integrating evolutionary models and transcription factor binding site models.
  • To assess the utility of genomic sequence alignments for regulatory motif discovery using comparative genomics.
  • To identify and predict novel cis-regulatory motifs in Saccharomyces cerevisiae and related species.

Main Methods:

  • Developed a probabilistic framework combining the HKY85 model of base substitution and weight matrix models for transcription factor binding sites.

Related Experiment Videos

  • Incorporated phylogenetic information and accounted for position-specific variations in binding sites.
  • Analyzed hexamers in yeast promoters to identify conserved sequences and reconstruct motifs.

    • Main Results:

    • Assessed the suitability of alignments for comparative genomic regulatory motif finding.
    • Identified conserved hexamers in Saccharomyces cerevisiae promoters.
    • Reconstructed known cis-regulatory motifs and predicted novel ones.
    • Experimentally validated a novel predicted regulatory element involved in glucose response.

    Conclusions:

    • The developed framework is a valuable tool for regulatory motif discovery.
    • The experimental validation highlights the approach's effectiveness in identifying functional elements missed by other methods.