Distinctions in the specificity of E2F function revealed by gene expression signatures.
The E2F family of transcription factors provides essential activities for coordinating the control of cellular proliferation and cell fate. Both E2F1 and E2F3 proteins have been shown to be particularly important for cell proliferation, whereas the E2F1 protein has the capacity to promote apoptosis. To explore the basis for this specificity of function, we used DNA microarray analysis to probe for the distinctions in the two E2F activities. Gene expression profiles that distinguish either E2F1- or E2F3-expressing cells from quiescent cells are enriched in genes encoding cell cycle and DNA replication activities, consistent with many past studies. E2F1 profile is also enriched in genes known to function in apoptosis. We also identified patterns of gene expression that specifically differentiate the activity of E2F1 and E2F3; this profile is enriched in genes known to function in mitosis. The specificity of E2F function has been attributed to protein interactions mediated by the marked box domain, and we now show that chimeric E2F proteins generate expression signatures that reflect the origin of the marked box, thus linking the biochemical mechanism for specificity of function with specificity of gene activation.
Black
Esther P
EP
Duke Institute for Genome Sciences and Policy, Department of Molecular Genetics and Microbiology, Medical Center, Duke University, Durham, NC 27710, USA.
Hallstrom
Timothy
T
Dressman
Holly K
HK
West
Mike
M
Nevins
Joseph R
JR
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D004261:DNA Replication / Q000235:genetics; D050684:E2F Transcription Factors / Q000235:genetics / Q000502:physiology*; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000502:physiology; D050703:E2F2 Transcription Factor / Q000235:genetics / Q000502:physiology; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D008938:Mitosis / Q000235:genetics; D015533:Transcriptional Activation
D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; D050699:E2F3 Transcription Factor; C493754:E2f1 protein, mouse; C484940:E2f2 protein, mouse; C490840:E2f3 protein, mouse