Significant improvement of reprogramming efficiency by transient overexpression of ZGA inducer Dux but not Dppa2/4

Cloned animal have been reported by somatic cell nuclear transfer (SCNT) for many years. However, the SCNT biotechnology is extremely inefficient, and zygotic genome activation (ZGA) is required for SCNT and chemical mediated somatic cell reprogramming. To identify candidate factors that facilitate ZGA in SCNT reprogramming, we carried out a siRNA-repressor and mRNA-inducer screening in SCNT to identify epigenetic and chromatin regulators of the ZGA transcriptional program. Through a series of experiments, we demonstrate that transient overexpression of Dux not only improved SCNT efficiency, but also increased the efficiency of chemical reprogramming. Furthermore, transient overexpression of Dux combined with inactivation of DNA methyltransferases (Dnmts) further promote the overall development of SCNT-derived animals. These findings enhance our understanding of ZGA-regulators in SCNT and chemical mediated somatic cell reprogramming, and suggest that transient overexpression of Dux may serve as a useful tool to enhances the somatic reprogramming efficiency.