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Related Experiment Videos

Modeling an evolutionary conserved circadian cis-element.

Eric R Paquet1, Guillaume Rey, Felix Naef

  • 1Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.

Plos Computational Biology
|February 20, 2008
PubMed
Summary
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Researchers developed a computational model to predict circadian gene targets. This model identifies cis-regulatory elements bound by CLOCK/CYCLE (CLK/CYC) and CLOCK/BMAL1 transcription factors, improving our understanding of circadian rhythms.

Area of Science:

  • Chronobiology
  • Genomics
  • Molecular Biology

Background:

  • Circadian rhythms are regulated by transcription factors like CLOCK/CYCLE (CLK/CYC) in insects and CLOCK/BMAL1 in mammals.
  • Predicting the specific DNA sequences targeted by these factors has been challenging due to limited understanding of their binding affinities beyond the E-box motif.

Purpose of the Study:

  • To develop a computational model for predicting cis-regulatory elements bound by CLK/CYC and CLOCK/BMAL1 transcription factors.
  • To identify novel circadian gene targets by analyzing conserved sequence elements across species.

Main Methods:

  • Comparative genomics was used to study conserved enhancer elements in Drosophila melanogaster.
  • A probabilistic sequence model was trained using known CLK/CYC target genes and validated with functional genomics data.

Related Experiment Videos

  • The model was applied to the mouse genome to identify CLOCK/BMAL1 targets and analyze their circadian phase.

    • Main Results:

    • A conserved 69-bp element upstream of the Drosophila period gene, containing two E-box-like motifs, was identified as a key feature.
    • The developed probabilistic model accurately predicted CLK/CYC and CLOCK/BMAL1 target genes.
    • Predicted targets showed enrichment in genes regulated by CLOCK/BMAL1, and their predicted phases in mouse liver aligned with known circadian regulation.

    Conclusions:

    • A predictive model for CLK/CYC and CLOCK/BMAL1-bound cis-enhancers was successfully built by integrating comparative and functional genomics data.
    • The findings suggest that the association between the CLOCK/BMAL1 complex and circadian cis-elements predates the divergence of insects and vertebrates.
    • This model provides a valuable tool for deciphering the regulatory networks of circadian oscillators.