Mouse development with a single E2F activator.
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.
Tsai
Shih-Yin
SY
Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA.
Opavsky
Rene
R
Sharma
Nidhi
N
Wu
Lizhao
L
Naidu
Shan
S
Nolan
Eric
E
Feria-Arias
Enrique
E
Timmers
Cynthia
C
Opavska
Jana
J
de Bruin
Alain
A
Chong
Jean-Leon
JL
Trikha
Prashant
P
Fernandez
Soledad A
SA
Stromberg
Paul
P
Rosol
Thomas J
TJ
Leone
Gustavo
G
D000818:Animals; D002478:Cells, Cultured; D050684:E2F Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050687:E2F1 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050703:E2F2 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050699:E2F3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D020964:Embryo Loss / Q000235:genetics; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D017353:Gene Deletion; D005838:Genotype; D006128:Growth / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; D050699:E2F3 Transcription Factor; C493754:E2f1 protein, mouse; C484940:E2f2 protein, mouse; C490840:E2f3 protein, mouse