Distinctions in the specificity of E2F function revealed by gene expression signatures

^*Duke Institute for Genome Sciences and Policy, ^†Department of Molecular Genetics and Microbiology, Medical Center, and ^§Institute for Statistics and Decision Sciences, Duke University, Durham, NC 27710

Edited by Ed Harlow, Harvard Medical School, Boston, MA (received for review May 25, 2005)

Abstract

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.

Footnotes

↵ ¶ To whom correspondence should be addressed. E-mail: j.nevins{at}duke.edu.
↵ ‡ Present address: Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536.
Author contributions: E.P.B., M.W., and J.R.N. designed research; E.P.B. and T.H. performed research; E.P.B., H.D., M.W., and J.R.N. analyzed data; and E.P.B., M.W., and J.R.N. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: MEF, mouse embryo fibroblast; HA, hemagglutinin; CMV, cytomegalovirus; Ad, adenovirus.