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Atypical E2F Repressors and Activators Coordinate Placental Development

2012; Elsevier BV; Volume: 22; Issue: 4 Linguagem: Inglês

10.1016/j.devcel.2012.01.013

1878-1551

Madhu M. Ouseph, Jing Li, Hui-Zi Chen, Thierry Pécot, Pamela L. Wenzel, J. Thompson, Grant Comstock, Veda Chokshi, Morgan Byrne, Braxton Forde, Jean-Leon Chong, Kun Huang, Raghu Machiraju, Alain de Bruin, Gustavo Leone,

Prenatal Screening and Diagnostics

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.