Atypical E2F repressors and activators coordinate placental development

Dev Cell. 2012 Apr 17;22(4):849-62. doi: 10.1016/j.devcel.2012.01.013.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Blotting, Western
  • Cell Proliferation
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • E2F3 Transcription Factor / genetics
  • E2F3 Transcription Factor / metabolism
  • E2F7 Transcription Factor / physiology*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism*
  • Embryonic Development / physiology*
  • Female
  • Gene Expression Profiling
  • Genes, Lethal
  • Integrases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Placentation / physiology*
  • Pregnancy
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Biomarkers
  • E2F3 Transcription Factor
  • E2F7 Transcription Factor
  • E2F8 protein, mouse
  • E2f7 protein, mouse
  • RNA, Messenger
  • Repressor Proteins
  • Cre recombinase
  • Integrases

Associated data

  • GEO/GSE30488