来自哈佛大学医学院的张毅研究组近期发现，DUX缺失会轻微引起合子基因组激活，但不影响小鼠发育。2019年6月出版的《Nature Genetics》杂志发表了这一最新研究成果。

卵细胞内的母源因子如何触发合子基因组激活（ZGA）一直是发育生物学中由来已久的问题。近期在2细胞态的胚胎干细胞研究中发现，DUX家族的转录因子是胎盘哺乳动物中负责ZGA的主要调控者。

为验证DUX在ZGA中的作用，研究人员建立了Dux基因簇敲除的小鼠品系。出乎意料的是，不管是在合子内敲除Dux还是在母体以及合子内均敲除Dux，这些胚胎仅表现出一定的发育潜能缺陷但均能长到成年。进一步通过对母体以及合子均敲除Dux的胚胎进行转录组测序，研究人员发现DUX的缺失对ZGA仅有微小影响，并且绝大多数2细胞态的DUX靶基因能够正常激活。因此，这项工作挑战了前人所建立的DUX在包括2细胞态在内的功能，并发现DUX对ZGA仅有轻微作用而且不影响小鼠发育。

附：英文原文

Title: Loss of DUX causes minor defects in zygotic genome activation and is compatible with mouse development

Author: Zhiyuan Chen, Yi Zhang

Issue&Volume: Volume 51 Issue 6, June 2019

Abstract: 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 mammals1,2. 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.

DOI: 10.1038/s41588-019-0418-7

Source:https://www.nature.com/articles/s41588-019-0418-7