title: Atypical E2F repressors and activators coordinate placental development.
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.
authors.affiliation: Solid Tumor Biology Program, Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Madhu M
authors.initials: MM
authors.lastname: Ouseph
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Hui-Zi
authors.initials: HZ
authors.lastname: Chen
authors.forename: Thierry
authors.initials: T
authors.lastname: Pécot
authors.forename: Pamela
authors.initials: P
authors.lastname: Wenzel
authors.forename: John C
authors.initials: JC
authors.lastname: Thompson
authors.forename: Grant
authors.initials: G
authors.lastname: Comstock
authors.forename: Veda
authors.initials: V
authors.lastname: Chokshi
authors.forename: Morgan
authors.initials: M
authors.lastname: Byrne
authors.forename: Braxton
authors.initials: B
authors.lastname: Forde
authors.forename: Jean-Leon
authors.initials: JL
authors.lastname: Chong
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.forename: Raghu
authors.initials: R
authors.lastname: Machiraju
authors.forename: Alain
authors.initials: A
authors.lastname: de Bruin
authors.forename: Gustavo
authors.initials: G
authors.lastname: Leone
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050702:E2F7 Transcription Factor / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D005804:Genes, Lethal; D019426:Integrases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010929:Placentation / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D050699:E2F3 Transcription Factor; D050702:E2F7 Transcription Factor; C504722:E2F8 protein, mouse; C479901:E2f7 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; C045073:Cre recombinase; D019426:Integrases