Title | Atypical E2F repressors and activators coordinate placental development. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Ouseph MM, Li J, Chen H-Z, Pécot T, Wenzel P, Thompson JC, Comstock G, Chokshi V, Byrne M, Forde B, Chong J-L, Huang K, Machiraju R, de Bruin A, Leone G |
Journal | Dev Cell |
Volume | 22 |
Issue | 4 |
Pagination | 849-62 |
Date Published | 2012 Apr 17 |
ISSN | 1878-1551 |
Keywords | Animals, Biomarkers, Blotting, Western, Cell Proliferation, Cells, Cultured, Chromatin Immunoprecipitation, E2F3 Transcription Factor, E2F7 Transcription Factor, Embryo, Mammalian, Embryonic Development, Female, Gene Expression Profiling, Genes, Lethal, Integrases, Mice, Mice, Inbred C57BL, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Placentation, Pregnancy, Real-Time Polymerase Chain Reaction, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger |
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. |
DOI | 10.1016/j.devcel.2012.01.013 |
Alternate Journal | Dev Cell |
PubMed ID | 22516201 |
Grant List | R01HD047470 / HD / NICHD NIH HHS / United States R01CA82259 / CA / NCI NIH HHS / United States R01CA85619 / CA / NCI NIH HHS / United States P01CA097189 / CA / NCI NIH HHS / United States |
Related Faculty:
Madhu Ouseph, M.D., Ph.D.