Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development. Dev Cell 2008 Jan;14(1):62-75
Date
01/16/2008Pubmed ID
18194653Pubmed Central ID
PMC2253677DOI
10.1016/j.devcel.2007.10.017Scopus ID
2-s2.0-37749005850 (requires institutional sign-in at Scopus site) 189 CitationsAbstract
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.
Author List
Li J, Ran C, Li E, Gordon F, Comstock G, Siddiqui H, Cleghorn W, Chen HZ, Kornacker K, Liu CG, Pandit SK, Khanizadeh M, Weinstein M, Leone G, de Bruin AAuthors
Hui-Zi Chen PhD, MD Assistant Professor in the Medicine department at Medical College of WisconsinGrant T. Comstock MD Assistant Professor in the Emergency Medicine department at Medical College of Wisconsin
Gustavo Leone PhD Senior Associate Dean, Center Director, Professor in the Pathology and Laboratory Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Camptothecin
Cell Survival
DNA Damage
DNA-Binding Proteins
Dimerization
E2F7 Transcription Factor
Embryonic Development
Mice
Mice, Knockout
Repressor Proteins
Transcription, Genetic
