De Iaco Alberto, Planet Evarist, Coluccio Andrea, Verp Sonia, Duc Julien, Trono Didier
School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Nat Genet. 2017 Jun;49(6):941-945. doi: 10.1038/ng.3858. Epub 2017 May 1.
In animal embryos, transcription is mostly silent for several cell divisions, until the release of the first major wave of embryonic transcripts through so-called zygotic genome activation (ZGA). Maternally provided ZGA-triggering factors have been identified in Drosophila melanogaster and Danio rerio, but their mammalian homologs are still undefined. Here, we provide evidence that the DUX family of transcription factors is essential to this process in mice and potentially in humans. First, human DUX4 and mouse Dux are both expressed before ZGA in their respective species. Second, both orthologous proteins bind the promoters of ZGA-associated genes and activate their transcription. Third, Dux knockout in mouse embryonic stem cells (mESCs) prevents the cells from cycling through a 2-cell-like state. Finally, zygotic depletion of Dux leads to impaired early embryonic development and defective ZGA. We conclude that DUX-family proteins are key inducers of zygotic genome activation in placental mammals.
在动物胚胎中，转录在最初几次细胞分裂期间大多处于沉默状态，直到通过所谓的合子基因组激活（ZGA）释放出第一波主要的胚胎转录本。在黑腹果蝇和斑马鱼中已鉴定出母体提供的ZGA触发因子，但其哺乳动物同源物仍未明确。在这里，我们提供证据表明，转录因子DUX家族对小鼠乃至可能对人类的这一过程至关重要。首先，人类DUX4和小鼠Dux在各自物种的ZGA之前均有表达。其次，两种直系同源蛋白均与ZGA相关基因的启动子结合并激活其转录。第三，小鼠胚胎干细胞（mESC）中的Dux基因敲除可阻止细胞进入类似二细胞的状态循环。最后，合子中Dux的缺失会导致早期胚胎发育受损和ZGA缺陷。我们得出结论，DUX家族蛋白是胎盘哺乳动物合子基因组激活的关键诱导因子。
