The identification of E2F1-specific target genes

Julie Wells, Carrie R. Graveel, Stephanie M. Bartley, Steven J. Madore, Peggy J. Farnham

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

The E2F family of transcriptional regulators consists of six different members. Analysis of E2F-regulated promoters by using cultured cells suggests that E2Fs may have redundant functions. However, animal studies have shown that loss of individual E2Fs can have distinct biological consequences. Such seemingly conflicting results could be due to a difference in E2F-mediated regulation in cell culture vs. animals. Alternatively, there may be genes that are specifically regulated by an individual E2F which have not yet been identified. To investigate this possibility further, we have analyzed gene expression in E2F1 nullizygous mice. We found that loss of E2F1 did not cause changes in expression of known E2F target genes, suggesting that perhaps E2F1-specific promoters are distinct from known E2F target promoters. Therefore, we used oligonucleotide microarrays to identify mRNAs whose expression is altered on loss of E2F1. We demonstrate by chromatin immunoprecipitation that several of the promoters that drive expression of the deregulated mRNAs selectively recruit E2F1, but not other E2Fs, and this recruitment is via an element distinct from a consensus E2F binding site. To our knowledge, these are as yet undocumented examples of promoters being occupied in asynchronously growing cells by a single E2F family member. Interestingly, the E2F1-specific target genes that we identified encode proteins having functions quite different from the function of known E2F target genes. Thus, whereas E2F1 may share redundant functions in cell growth control with other E2F family members, it may also play an important biological role distinct from the other E2Fs.

Original languageEnglish (US)
Pages (from-to)3890-3895
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number6
DOIs
StatePublished - Mar 19 2002
Externally publishedYes

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Genes
Messenger RNA
Chromatin Immunoprecipitation
Oligonucleotide Array Sequence Analysis
Cultured Cells
Consensus
Cell Culture Techniques
Binding Sites
Gene Expression
Growth
Proteins
Drive

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The identification of E2F1-specific target genes. / Wells, Julie; Graveel, Carrie R.; Bartley, Stephanie M.; Madore, Steven J.; Farnham, Peggy J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 6, 19.03.2002, p. 3890-3895.

Research output: Contribution to journalArticle

Wells, Julie ; Graveel, Carrie R. ; Bartley, Stephanie M. ; Madore, Steven J. ; Farnham, Peggy J. / The identification of E2F1-specific target genes. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 6. pp. 3890-3895.
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