Oct-4 Regulates The Transcription Of DNA Methyltransferase 1 (Dnmt1) Promoter In The Preimplantation Embryo Of Mouse

In the process of preimplantation embryo development in mammals, epigenetic modification plays an important role. Studies show that DNA methylation, non-coding RNA, histone modification and chromatin remodeling belong to the mechanism of epigenetic modifications. In many epigenetic modifications mode, DNA methylation is the most widely and most fully epigenetic modification of the model. In the process of embryonic development, within the scope of whole genome DNA methylation patterns of change and maintain was conducted through DNA methylation transferase. It is well known that DNA methylation transferase in mammalian body there are three main types: Dnmtl, Dnmt3a and Dnmt3b.Genome-wide change of DNA methylation maintained by Dnmtl is an important event during mammalian embryonic development. On the other hand, the role of key development-related gene, Oct-4, in mouse preimplantaion embryo development has been demonstrated in many previous studies. However, the correlation between DNA methylation and Oct-4 in this specific process remains unclear. In the present study, Kumming white mouse was used as a model and the expression of Dnmtl in the preimplantaion embryos was studied by real-time PCR, exhibiting an inverse pattern when compared with the level of Oct-4 as reported. Promoter assay was performed to explore the promoter activity of Dnmtl when co-transfected with eukaryotic expression recombinant plasmid containing mouse Oct-4 in NIH/3T3 cells. The results showed that the activity of Dnmtl promoter was down-regulated by Oct-4 when lacking of-554 to-294 bp region relative to TSS. Chip and EMSA further demonstrated the binding of Oct-4 to the Dnmtl promoter in vivo and in vitro. Overexpression of mouse Oct-4 in NCI-H157 cells further up-regulated the expression and enzyme activity of Dnmtl. Taken together, these data indicate that mouse Dnmtl expression is regulated by Oct-4 through directly binding to specific site on Dnmtl promoter. These findings suggested that Oct-4 is involved in the transcription of Dnmtl and further regulated the DNA methylation state of the genome. The expression of Dnmtl in turn influenced DNA methylation status of 5’-flanking region of the Oct-4 and other development-related genes during early stage of mammalian embryonic development.