Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Nat Genet. 2019 Jun;51(6):947-951. doi: 10.1038/s41588-019-0418-7. Epub 2019 May 27.
How maternal factors in oocytes trigger zygotic genome activation (ZGA) is a long-standing question in developmental biology. Recent studies in 2-cell-like embryonic stem cells (2C-like cells) suggest that transcription factors of the DUX family are key regulators of ZGA in placental mammals. To characterize the role of DUX in ZGA, we generated Dux cluster knockout (KO) mouse lines. Unexpectedly, we found that both Dux zygotic KO (Z-KO) and maternal and zygotic KO (MZ-KO) embryos can survive to adulthood despite showing reduced developmental potential. Furthermore, transcriptome profiling of the MZ-KO embryos revealed that loss of DUX has minimal effects on ZGA and most DUX targets in 2C-like cells are normally activated in MZ-KO embryos. Thus, contrary to the key function of DUX in inducing 2C-like cells, our data indicate that DUX has only a minor role in ZGA and that loss of DUX is compatible with mouse development.
卵母细胞中的母体因素如何触发合子基因组激活（ZGA）是发育生物学中的一个长期存在的问题。最近在 2 细胞样胚胎干细胞（2C-like cells）中的研究表明，DUX 家族的转录因子是胎盘哺乳动物 ZGA 的关键调节剂。为了表征 DUX 在 ZGA 中的作用，我们生成了 Dux 簇敲除（KO）小鼠品系。出乎意料的是，我们发现尽管 Dux 合子 KO（Z-KO）和母源和合子 KO（MZ-KO）胚胎的发育潜力降低，但它们都能存活到成年。此外，MZ-KO 胚胎的转录组谱分析表明，DUX 的缺失对 ZGA 的影响很小，并且在 2C-like 细胞中大多数 DUX 靶基因在 MZ-KO 胚胎中正常激活。因此，与 DUX 在诱导 2C-like 细胞中的关键功能相反，我们的数据表明 DUX 在 ZGA 中仅起次要作用，并且 DUX 的缺失与小鼠发育相容。
