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Compensation and specificity of function within the E2F family

Oncogene volume 26, pages 321–327 (2007)Cite this article

Abstract

Functions encoded by single genes in lower organisms are often represented by multiple related genes in the mammalian genome. An example is the retinoblastoma and E2F families of proteins that regulate transcription during the cell cycle. Analysis of gene function using germline mutations is often confounded by overlapping function resulting in compensation. Indeed, in cells deleted of the E2F1 or E2F3 genes, there is an increase in the expression of the other family member. To avoid complications of compensatory effects, we have used small-interfering RNAs that target individual E2F proteins to generate a temporary loss of E2F function. We find that both E2F1 and E2F3 are required for cells to enter the S phase from a quiescent state, whereas only E2F3 is necessary for the S phase in growing cells. We also find that the acute loss of E2F3 activity affects the expression of genes encoding DNA replication and mitotic activities, whereas loss of E2F1 affects a limited number of genes that are distinct from those regulated by E2F3. We conclude that the long-term loss of E2F activity does lead to compensation by other family members and that the analysis of acute loss of function reveals specific and distinct roles for these proteins.

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Acknowledgements

We thank Drs David Turner and Yang Shi for providing U6 promoter and technical advices. We thank Dr Rachel Rempel for providing MEFs. This work was supported by grants from the NIH (CA104663, CA106520, CA112952). Finally, we thank Kaye Culler for her assistance in the preparation of the manuscript.

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Authors and Affiliations

  1. Department of Molecular Genetics and Microbiology, Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, NC, USA

    L-J Kong, J T Chang, A H Bild & J R Nevins

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  1. L-J Kong
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  2. J T Chang
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  4. J R Nevins
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Correspondence to J R Nevins.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Kong, LJ., Chang, J., Bild, A. et al. Compensation and specificity of function within the E2F family. Oncogene 26, 321–327 (2007). https://doi.org/10.1038/sj.onc.1209817

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