Atypical E2F Repressors and Activators Coordinate Placental Development

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Abstract

The evolutionarily ancient arm of the . E2f family of transcription factors consisting of the two atypical members . E2f7 and . E2f8 is essential for murine embryonic development. However, the critical tissues, cellular processes, and molecular pathways regulated by these two factors remain unknown. Using a series of fetal and placental lineage-specific . cre mice, we show that E2F7/E2F8 functions in extraembryonic trophoblast lineages are both necessary and sufficient to carry fetuses to term. Expression profiling and biochemical approaches exposed the canonical E2F3a activator as a key family member that antagonizes E2F7/E2F8 functions. Remarkably, the concomitant loss of . E2f3a normalized placental gene expression programs, corrected placental defects, and fostered the survival of . E2f7/. E2f8-deficient embryos to birth. In summary, we identified a placental transcriptional network tightly coordinated by activation and repression through two distinct arms of the E2F family that is essential for extraembryonic cell proliferation, placental development, and fetal viability. E2F transcriptional control of the cell cycle is traditionally described in terms of E2F1-3 as activators and E2F4-6 as complementary repressors. Ouseph et al. show that a key repressive function is instead mediated by the atypical repressors E2F7/8; genetic deletion of E2F3a rescues E2F7/8 double-mutant phenotypes. © 2012 Elsevier Inc.

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Ouseph, M. M., Li, J., Chen, H. Z., Pécot, T., Wenzel, P., Thompson, J. C., … Leone, G. (2012). Atypical E2F Repressors and Activators Coordinate Placental Development. Developmental Cell, 22(4), 849–862. https://doi.org/10.1016/j.devcel.2012.01.013

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