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Atypical E2F repressors and activators coordinate placental development.

Madhu M Ouseph | Jing Li | Hui-Zi Chen | Thierry Pécot | Pamela Wenzel | John C Thompson | Grant Comstock | Veda Chokshi | Morgan Byrne | Braxton Forde | Jean-Leon Chong | Kun Huang | Raghu Machiraju | Alain de Bruin | Gustavo Leone
Developmental cell | 2012

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.

Pubmed ID: 22516201

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Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: R01HD047470
  • Agency: NCI NIH HHS, United States
    Id: P01 CA097189
  • Agency: NCI NIH HHS, United States
    Id: R01 CA085619
  • Agency: NCI NIH HHS, United States
    Id: R01 CA082259
  • Agency: NCI NIH HHS, United States
    Id: R01CA82259
  • Agency: NCI NIH HHS, United States
    Id: R01CA85619
  • Agency: NCI NIH HHS, United States
    Id: P01CA097189
  • Agency: NCI NIH HHS, United States
    Id: R01 CA082259-05
  • Agency: NCI NIH HHS, United States
    Id: R01 CA085619-05
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD047470
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD047470-05

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