1. Canonical and atypical E2Fs regulate the mammalian endocycle.
- Author
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Chen HZ, Ouseph MM, Li J, Pécot T, Chokshi V, Kent L, Bae S, Byrne M, Duran C, Comstock G, Trikha P, Mair M, Senapati S, Martin CK, Gandhi S, Wilson N, Liu B, Huang YW, Thompson JC, Raman S, Singh S, Leone M, Machiraju R, Huang K, Mo X, Fernandez S, Kalaszczynska I, Wolgemuth DJ, Sicinski P, Huang T, Jin V, and Leone G
- Subjects
- Animals, Cell Cycle genetics, Chromatin Immunoprecipitation, E2F Transcription Factors genetics, E2F1 Transcription Factor genetics, E2F1 Transcription Factor metabolism, E2F2 Transcription Factor genetics, E2F2 Transcription Factor metabolism, E2F3 Transcription Factor genetics, E2F3 Transcription Factor metabolism, E2F7 Transcription Factor genetics, E2F7 Transcription Factor metabolism, Female, Flow Cytometry, Giant Cells cytology, Giant Cells metabolism, Hepatocytes cytology, Hepatocytes metabolism, Immunohistochemistry, Mice, Microscopy, Confocal, Microscopy, Electron, Transmission, Microscopy, Fluorescence, Pregnancy, Repressor Proteins genetics, Repressor Proteins metabolism, Trophoblasts metabolism, Cell Cycle physiology, E2F Transcription Factors metabolism
- Abstract
The endocycle is a variant cell cycle consisting of successive DNA synthesis and gap phases that yield highly polyploid cells. Although essential for metazoan development, relatively little is known about its control or physiologic role in mammals. Using lineage-specific cre mice we identified two opposing arms of the E2F program, one driven by canonical transcription activation (E2F1, E2F2 and E2F3) and the other by atypical repression (E2F7 and E2F8), that converge on the regulation of endocycles in vivo. Ablation of canonical activators in the two endocycling tissues of mammals, trophoblast giant cells in the placenta and hepatocytes in the liver, augmented genome ploidy, whereas ablation of atypical repressors diminished ploidy. These two antagonistic arms coordinate the expression of a unique G2/M transcriptional program that is critical for mitosis, karyokinesis and cytokinesis. These results provide in vivo evidence for a direct role of E2F family members in regulating non-traditional cell cycles in mammals.
- Published
- 2012
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