双细胞样（2C样）胚胎干细胞（ESC）是一小群ESC自发表达合子基因组激活（ZGA）基因和重复序列，如Zscan4和带亮氨酸的鼠内源性逆转录病毒（MERVL），并在2细胞期小鼠胚胎中特异性表达。尽管许多类型的治疗和药物可以提升ESC向2C样ESC的转变，Dux通过直接增加Zscan4和MERVL的表达而作为这种转变的关键因素。然而,Dux的丢失并没有损害老鼠的出生，这表明Dux可能不是受精胚胎的主要过渡因素。据报道，对于来自体细胞核移植（SCNT）的2细胞胚胎，其ZGA基因和重复序列的表达异常，Dux通过其C端结构域纠正异常的H3K9ac修饰来提高重编程效率。我们证实，SCNT胚胎中全长DuxmRNA的过表达提高了植入前发育的效率（62.16％vs.相对于对照为41.26%），并且还增加了Zscan4和MERVL的表达。此外，我们发现Dux的N端双同源域对于Dux的定位和功能是必不可少的。中间区域是MERVL和Zscan4激活所必需的，C端结构域对提高H3K27ac的水平很重要。含有具有中间区域或C末端结构域的N末端双同源结构域的突变体DuxmRNA也改善了SCNT胚胎的植入前发育。这是第一份专注于区分源自SCNT的胚胎中Dux的功能域的报告。
Two-cell-like (2C-like) embryonic stem cells (ESCs) are a small group of ESCs that spontaneously express zygotic genome activation (ZGA) genes and repeats, such as Zscan4 and murine endogenous retrovirus with leucine (MERVL), and are specifically expressed in 2-cell-stage mouse embryos. Although numerous types of treatment and agents elevate the transition of ESCs to 2C-like ESCs, Dux serves as a critical factor in this transition by increasing the expression of Zscan4 and MERVL directly. However, the loss of Dux did not impair the birth of mice, suggesting that Dux may not be the primary transitioning factor in fertilized embryos. It has been reported that for 2-cell embryos derived from somatic cell nuclear transfer (SCNT) and whose expression of ZGA genes and repeats was aberrant, Dux improved the reprogramming efficiency by correcting aberrant H3K9ac modification via its C-terminal domain. We confirmed that the overexpression of full-length Dux mRNA in SCNT embryos improved the efficiency of preimplantation development (62.16% vs. 41.26% with respect to controls) and also increased the expression of Zscan4 and MERVL. Furthermore, we found that the N-terminal double homeodomains of Dux were indispensable for Dux localization and function. The intermediate region was essential for MERVL and Zscan4 activation, and the C-terminal domain was important for elevating level of H3K27ac. Mutant Dux mRNA containing N-terminal double homeodomains with the intermediate region or the C-terminal domain also improved the preimplantation development of SCNT embryos. This is the first report focusing on distinguishing functional domains of Dux in embryos derived from SCNT.
