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PMID: 18594513 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Mouse development with a single E2F activator.

Nature ·Vol. 454 ·No. 7208 ·2008-08-28 ·Pages 1137-41

Tsai SY, Opavsky R, Sharma N, Wu L, Naidu S, Nolan E, Feria-Arias E, Timmers C, Opavska J, de Bruin A, Chong JL, Trikha P, Fernandez SA, Stromberg P, Rosol TJ, Leone G

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 (E2f3a(3bki) 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.

MeSH Terms
Animals Cells, Cultured E2F Transcription Factors/deficiency,genetics,metabolism E2F1 Transcription Factor/deficiency,genetics,metabolism E2F2 Transcription Factor/deficiency,genetics,metabolism E2F3 Transcription Factor/deficiency,genetics,metabolism Embryo Loss/genetics Embryo, Mammalian/embryology,metabolism Embryonic Development/genetics Gene Deletion Genotype Growth/genetics Mice Mice, Knockout Phenotype
Chemicals
E2F Transcription Factors E2F1 Transcription Factor E2F2 Transcription Factor E2F3 Transcription Factor E2f1 protein, mouse E2f2 protein, mouse E2f3 protein, mouse
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Tsai Shih-Yin
Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA.
Opavsky Rene
Sharma Nidhi
Wu Lizhao
Naidu Shan
Nolan Eric
Feria-Arias Enrique
Timmers Cynthia
Opavska Jana
de Bruin Alain
Chong Jean-Leon
Trikha Prashant
Fernandez Soledad A
Stromberg Paul
Rosol Thomas J
Leone Gustavo
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature07066
Published
2008-08-28
Epub
2008-00-25
Pages
1137-41
Language
English
Region
England
NLM ID
0410462
PMCID
PMC4288824
Subset
IM
Grants
NICHD NIH HHS · R01HD047470 · United States
NCI NIH HHS · P01 CA097189 · United States
NCI NIH HHS · R01 CA085619 · United States
NCI NIH HHS · R01CA121275 · United States
NICHD NIH HHS · R01 HD047470 · United States
NCI NIH HHS · K01 CA102328 · United States
NICHD NIH HHS · R01HD042619 · United States
NCI NIH HHS · R01CA85619 · United States
NCI NIH HHS · R01 CA121275-03 · United States
NCI NIH HHS · T32CA106196 · United States
NCI NIH HHS · P01CA097189 · United States
NCI NIH HHS · R01 CA121275 · United States
NCI NIH HHS · T32 CA106196 · United States
NICHD NIH HHS · R01 HD042619 · United States
NCI NIH HHS · K01CA102328 · United States
External Links
PubMed source DOI: 10.1038/nature07066 PMC Full Text View journal details
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