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Molecular and Cellular Biology, January 2009, p. 414-424, Vol. 29, No. 2
0270-7306/09/$08.00+0     doi:10.1128/MCB.01161-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

E2f3a and E2f3b Contribute to the Control of Cell Proliferation and Mouse Development{triangledown} ,{dagger}

Jean-Leon Chong,1,2,3 Shih-Yin Tsai,1,2,3 Nidhi Sharma,1,2,3 Rene Opavsky,1,2,3 Richard Price,1,2,3 Lizhao Wu,1,2,3,{ddagger} Soledad A. Fernandez,4 and Gustavo Leone1,2,3*

Human Cancer Genetics Program,1 Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine and Public Health,2 Department of Molecular Genetics, College of Biological Sciences,3 Center for Biostatistics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 432104

Received 22 July 2008/ Returned for modification 24 August 2008/ Accepted 4 November 2008

The E2f3 locus encodes two Rb-binding gene products, E2F3a and E2F3b, which are differentially regulated during the cell cycle and are thought to be critical for cell cycle progression. We targeted the individual inactivation of E2f3a or E2f3b in mice and examined their contributions to cell proliferation and development. Chromatin immunoprecipitation and gene expression experiments using mouse embryo fibroblasts deficient in each isoform showed that E2F3a and E2F3b contribute to G1/S-specific gene expression and cell proliferation. Expression of E2f3a or E2f3b was sufficient to support E2F target gene expression and cell proliferation in the absence of other E2F activators, E2f1 and E2f2, suggesting that these isoforms have redundant functions. Consistent with this notion, E2f3a–/– and E2f3b–/– embryos developed normally, whereas embryos lacking both isoforms (E2f3–/–) died in utero. We also find that E2f3a and E2f3b have redundant and nonredundant roles in the context of Rb mutation. Analysis of double-knockout embryos suggests that the ectopic proliferation and apoptosis in Rb–/– embryos is mainly mediated by E2f3a in the placenta and nervous system and by both E2f3a and E2f3b in lens fiber cells. Together, we conclude that the contributions of E2F3a and E2F3b in cell proliferation and development are context dependent.

* Corresponding author. Mailing address: Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Comprehensive Cancer Center, 460 W. 12th Ave., Columbus, OH 43210. Phone: (614) 688-4567. Fax: (614) 292-3312. E-mail: Gustavo.Leone{at}osumc.edu

{triangledown} Published ahead of print on 17 November 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Department of Cell Biology and Molecular Medicine and University Hospital Cancer Center, UMDNJ-New Jersey Medical School, Newark, NJ 07103.

Molecular and Cellular Biology, January 2009, p. 414-424, Vol. 29, No. 2
0270-7306/09/$08.00+0     doi:10.1128/MCB.01161-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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