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.
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.
E2f 家族转录因子的进化古老臂由两个非典型成员 E2f7 和 E2f8 组成，对于小鼠胚胎发育是必不可少的。然而，这些两个因素调节的关键组织、细胞过程和分子途径仍然未知。使用一系列胎儿和胎盘谱系特异性 cre 小鼠，我们表明 E2F7/E2F8 在胚胎外滋养层谱系中的功能对于将胎儿带到足月都是必需和充分的。表达谱分析和生化方法揭示了经典的 E2F3a 激活剂是拮抗 E2F7/E2F8 功能的关键家族成员。值得注意的是，同时缺失 E2f3a 使胎盘基因表达程序正常化，纠正了胎盘缺陷，并促进了 E2f7/E2f8 缺陷胚胎的存活至出生。总之，我们确定了一个胎盘转录网络，通过 E2F 家族的两个不同臂通过激活和抑制紧密协调，对于胚胎外细胞增殖、胎盘发育和胎儿存活是必不可少的。
