E2F基因家族被认为在调控细胞增殖过程中发挥至关重要作用。但目前还不清楚这些基因在动物体内是如何相互作用发挥功效的。近日,一项研究表明,两个E2F抑制基因对功能性胎盘发育以及平衡E2F激活基因的作用尤为重要。
据美国俄亥俄州立大学综合癌症中心、阿瑟詹姆斯克肿瘤医院和Richard J. Solove研究所研究人员完成的新研究证实:调控基因家族中的两个特殊的抑制基因对胎盘的发育过程中细胞的增殖至关重要。
这两个基因被称为E2F7和E2f8。干细胞不表达这些基因的话,胎盘由过度密集、缺乏组织结构的细胞组成,结果就是正常胚胎发育所需的氧气和营养物质不能正常输送。
但当胎盘干细胞缺少第三个基因即E2f3a激活基因的话,胎盘缺陷将得到纠正恢复,胚胎也会继续发育。
相关研究论文发表在Developmental Cell杂志上,研究揭示了E2Fs在分子水平是如何控制动物体内细胞的增殖,研究人员说。
这两个基因属于调控基因家族成员,在人类中,共有八名基因成员。研究人员认为激活或抑制其他基因控制正常细胞与癌细胞的细胞分裂和增殖。但是,基因之间是如何相互作用的却知之甚少。
Leone和他的同事们利用缺乏三个E2F基因中一个或多个基因的动物的滋养层干细胞开展研究。Leone说:该研究证实E2F7和E2f8抑制基因对完整的、功能性胎盘发育至关重要,这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