Journal Article

Canonical and atypical E2Fs regulate the mammalian endocycle

Sicinski, Piotr, Chen, Hui-Zi, Wilson, Nicholas, Mair, Markus, Leone, Gustavo, Chokshi, Veda, Mo, Xiaokui, Machiraju, Raghu, Leone, Marcelo, Liu, Bin, Comstock, Grant, Senapati, Shantibhusan, Gandhi, Sagar, Martin, Chelsea K., Bae, Sooin, Wolgemuth, Debra J., Jin, Victor, Huang, Yi-Wen, Singh, Shantanu, Li, Jing, Thompson, John C., Huang, Kun, Pécot, Thierry, Kent, Lindsey, Raman, Sundaresan, Duran, Camille, Kalaszczynska, Ilona, Huang, Tim, Byrne, Morgan, Trikha, Prashant, Fernandez, Soledad, Ouseph, Madhu M.

2012

Overview

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. In mammals, polyploidy is only seen in liver hepatocytes and in trophoblast giant cells in the placenta. Leone and colleagues now show that ploidy is controlled in an antagonistic fashion by canonical E2F transcriptional activators and atypical E2F7 and E2F8 repressors, through the control of G2/M-associated genes.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/208/742 / 631/80/641 / Ablation / Animals / Biology / Cancer / Cancer Research / Cell Biology / Cell cycle / Cell Cycle - genetics / Cell Cycle - physiology / Cell division / Chromatin Immunoprecipitation / Deoxyribonucleic acid / Developmental Biology / DNA / DNA synthesis / E2F Transcription Factors - genetics / E2F Transcription Factors - metabolism / 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 / Gene expression / Genetics / Genomes / Giant Cells - cytology / Giant Cells - metabolism / Gynecology / Hepatocytes - cytology / Hepatocytes - metabolism / Immunohistochemistry / Life Sciences / Liver / Mammals / Mice / Microscopy, Confocal / Microscopy, Electron, Transmission / Microscopy, Fluorescence / Obstetrics / Physiological aspects / Polyploidy / Pregnancy / Repressor Proteins - genetics / Repressor Proteins - metabolism / RNA polymerase / Stem Cells / Transcription factors / Trophoblasts - metabolism