E2F基因家族被認為在調(diào)控細胞增殖過程中發(fā)揮至關(guān)重要作用。但目前還不清楚這些基因在動物體內(nèi)是如何相互作用發(fā)揮功效的,。近日，一項研究表明,，兩個E2F抑制基因?qū)δ苄蕴ケP發(fā)育以及平衡E2F激活基因的作用尤為重要,。
據(jù)美國俄亥俄州立大學(xué)綜合癌癥中心、阿瑟詹姆斯克腫瘤醫(yī)院和Richard J. Solove研究所研究人員完成的新研究證實：調(diào)控基因家族中的兩個特殊的抑制基因?qū)μケP的發(fā)育過程中細胞的增殖至關(guān)重要,。
這兩個基因被稱為E2F7和E2f8,。干細胞不表達這些基因的話，胎盤由過度密集,、缺乏組織結(jié)構(gòu)的細胞組成,，結(jié)果就是正常胚胎發(fā)育所需的氧氣和營養(yǎng)物質(zhì)不能正常輸送。
但當胎盤干細胞缺少第三個基因即E2f3a激活基因的話,，胎盤缺陷將得到糾正恢復(fù),，胚胎也會繼續(xù)發(fā)育。
相關(guān)研究論文發(fā)表在Developmental Cell雜志上,，研究揭示了E2Fs在分子水平是如何控制動物體內(nèi)細胞的增殖，研究人員說,。
這兩個基因?qū)儆谡{(diào)控基因家族成員,，在人類中，共有八名基因成員,。研究人員認為激活或抑制其他基因控制正常細胞與癌細胞的細胞分裂和增殖,。但是,，基因之間是如何相互作用的卻知之甚少。
Leone和他的同事們利用缺乏三個E2F基因中一個或多個基因的動物的滋養(yǎng)層干細胞開展研究,。Leone說：該研究證實E2F7和E2f8抑制基因?qū)ν暾?、功能性胎盤發(fā)育至關(guān)重要，這些抑制基因也中和激活基因E2f3a的功效,。（生物谷：Bioon.com）
doi:10.1016/j.devcel.2012.01.013
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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
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
