Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development.
The E2f7 and E2f8 family members are thought to function as transcriptional repressors important for the control of cell proliferation. Here, we have analyzed the consequences of inactivating E2f7 and E2f8 in mice and show that their individual loss had no significant effect on development. Their combined ablation, however, resulted in massive apoptosis and dilation of blood vessels, culminating in lethality by embryonic day E11.5. A deficiency in E2f7 and E2f8 led to an increase in E2f1 and p53, as well as in many stress-related genes. Homo- and heterodimers of E2F7 and E2F8 were found on target promoters, including E2f1. Importantly, loss of either E2f1 or p53 suppressed the massive apoptosis in double-mutant embryos. These results identify E2F7 and E2F8 as a unique repressive arm of the E2F transcriptional network that is critical for embryonic development and control of the E2F1-p53 apoptotic axis.
Li
Jing
J
Department of Molecular Virology, The Ohio State University, Columbus, OH 43210, USA.
Ran
Cong
C
Li
Edward
E
Gordon
Faye
F
Comstock
Grant
G
Siddiqui
Hasan
H
Cleghorn
Whitney
W
Chen
Hui-Zi
HZ
Kornacker
Karl
K
Liu
Chang-Gong
CG
Pandit
Shusil K
SK
Khanizadeh
Mehrbod
M
Weinstein
Michael
M
Leone
Gustavo
G
de Bruin
Alain
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019281:Dimerization; D050702:E2F7 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D050702:E2F7 Transcription Factor; C504722:E2F8 protein, mouse; C479901:E2f7 protein, mouse; D012097:Repressor Proteins; D002166:Camptothecin