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Related Experiment Videos

The identification of E2F1-specific target genes.

Julie Wells1, Carrie R Graveel, Stephanie M Bartley

  • 1McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, WI 53706; and Genomics and Bioinformatics, Pfizer Inc., Ann Arbor, MI 48105.

Proceedings of the National Academy of Sciences of the United States of America
|March 21, 2002
PubMed
Summary

The E2F1 transcription factor has unique target genes distinct from other E2F family members. This finding reveals specific roles for E2F1 beyond shared functions in cell growth regulation.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • The E2F family of transcription factors plays crucial roles in cell cycle regulation.
  • Studies in cell culture suggest E2F members have redundant functions, but animal studies indicate distinct roles.
  • Conflicting data may arise from differences in regulation between cell culture and animal models, or from unidentified specific targets.

Purpose of the Study:

  • To investigate the existence of E2F1-specific target genes.
  • To identify genes regulated exclusively by E2F1 in vivo.
  • To understand the distinct biological functions of E2F1.

Main Methods:

  • Gene expression analysis in E2F1 nullizygous mice.
  • Oligonucleotide microarrays to identify differentially expressed mRNAs.

Related Experiment Videos

  • Chromatin immunoprecipitation (ChIP) to validate E2F1 binding to specific promoters.

    • Main Results:

    • Loss of E2F1 did not affect the expression of known E2F target genes.
    • Microarray analysis identified novel mRNAs deregulated in E2F1 nullizygous mice.
    • ChIP assays confirmed selective recruitment of E2F1, but not other E2Fs, to promoters of these novel target genes via a non-consensus binding element.
    • Identified E2F1-specific target genes encode proteins with functions distinct from known E2F targets.

    Conclusions:

    • E2F1 regulates a distinct set of target genes not shared with other E2F family members.
    • These E2F1-specific targets suggest unique biological roles for E2F1 beyond cell growth control.
    • This study provides evidence for promoter occupancy by a single E2F family member in asynchronously growing cells.