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Publication : Canonical and atypical E2Fs regulate the mammalian endocycle.

First Author  Chen HZ Year  2012
Journal  Nat Cell Biol Volume  14
Issue  11 Pages  1192-202
PubMed ID  23064266 Mgi Jnum  J:190713
Mgi Id  MGI:5449497 Doi  10.1038/ncb2595
Citation  Chen HZ, et al. (2012) Canonical and atypical E2Fs regulate the mammalian endocycle. Nat Cell Biol 14(11):1192-202
abstractText  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.
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