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Related Experiment Videos

Discovering functional transcription-factor combinations in the human cell cycle.

Zhou Zhu1, Jay Shendure, George M Church

  • 1Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. zhou-zhu@student.hms.harvard.edu

Genome Research
|June 3, 2005
PubMed
Summary

This study introduces a computational method to discover transcription-factor (TF) combinations by analyzing conserved sequences and gene expression data. It successfully identified known and novel TF associations, including a cell cycle regulatory module.

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Area of Science:

  • Computational biology
  • Genomics
  • Transcriptional regulation

Background:

  • High-throughput technologies enable in silico analysis of transcriptional regulation.
  • Previous studies primarily focused on lower eukaryotes.
  • Understanding transcription-factor (TF) combinations is crucial for deciphering gene regulation.

Purpose of the Study:

  • To develop and apply a computational approach for identifying functional TF combinations in higher eukaryotes.
  • To investigate the overrepresentation of TF binding sites and their impact on gene expression coherence.
  • To discover novel TF associations and regulatory modules without prior biological knowledge.

Main Methods:

  • Utilized phylogenetically conserved sequences and microarray expression data for in silico analysis.

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  • Incorporated orientational and positional constraints for TF binding site analysis.
  • Searched for overrepresented TF binding site combinations and their correlation with coherent expression profiles.

    • Main Results:

    • Discovered several experimentally validated and novel TF associations.
    • Identified a regulatory module controlling cell cycle-dependent transcription of G2-M genes.
    • Detected numerous homotypic TF combinations, highlighting the significance of binding-site density in higher eukaryotes.

    Conclusions:

    • The developed computational method effectively identifies functional TF combinations.
    • The study expands the understanding of transcriptional regulation in higher eukaryotes, including cell cycle control.
    • Binding-site density (homotypic combinations) plays a critical role in transcriptional regulation.