Mouse development with a single E2F activator

Shih Yin Tsai, Rene Opavsky, Nidhi Sharma, Lizhao Wu, Shan Naidu, Eric Nolan, Enrique Feria-Arias, Cynthia Timmers, Jana Opavska, Alain De Bruin, Jean Leon Chong, Prashant Trikha, Soledad A. Fernandez, Paul Stromberg, Thomas J. Rosol, Gustavo Leone

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

The E2F family is conserved from Caenorhabditis elegans to mammals, with some family members having transcription activation functions and others having repressor functions. Whereas C. elegans and Drosophila melanogaster have a single E2F activator protein and repressor protein, mammals have at least three activator and five repressor proteins. Why such genetic complexity evolved in mammals is not known. To begin to evaluate this genetic complexity, we targeted the inactivation of the entire subset of activators, E2f1, E2f2, E2f3a and E2f3b, singly or in combination in mice. We demonstrate that E2f3a is sufficient to support mouse embryonic and postnatal development. Remarkably, expression of E2f3b or E2f1 from the E2f3a locus (E2f3a3bki or E2f3a 1ki, respectively) suppressed all the postnatal phenotypes associated with the inactivation of E2f3a. We conclude that there is significant functional redundancy among activators and that the specific requirement for E2f3a during postnatal development is dictated by regulatory sequences governing its selective spatiotemporal expression and not by its intrinsic protein functions. These findings provide a molecular basis for the observed specificity among E2F activators during development.

Original languageEnglish (US)
Pages (from-to)1137-1141
Number of pages5
JournalNature
Volume454
Issue number7208
DOIs
StatePublished - Aug 28 2008

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    Tsai, S. Y., Opavsky, R., Sharma, N., Wu, L., Naidu, S., Nolan, E., Feria-Arias, E., Timmers, C., Opavska, J., De Bruin, A., Chong, J. L., Trikha, P., Fernandez, S. A., Stromberg, P., Rosol, T. J., & Leone, G. (2008). Mouse development with a single E2F activator. Nature, 454(7208), 1137-1141. https://doi.org/10.1038/nature07066