Oct-4 Regulates DNA Methyltransferase 1 (Dnmt1) Transcription by Direct Regulatory Element Binding

The transcription factor Oct4 plays a pivotal role for the development of mouse preimplantation embryo, and DNA methyltransferase 1 (Dnmt1) maintains the changes of DNA methylation during mammalian early embryonic development. However, little is known of the role of Oct4 in DNA methylation in mouse. In the present study, Kunming white mice were used as an animal model to elucidate the correlation between DNA methylation and Oct4 during mammalian embryonic development. The expression of Dnmt1 and Oct4 were initially studied by real-time PCR, exhibiting different patterns during mouse preimplantation stage. Moreover, by using promoter assay and Chip analysis, we found that the transcriptional activity of Dnmt1 in mouse NIH/3T3 cells and CCE cells were both regulated by Oct4 through direct binding to -554 to -294 fragment of upstream regulation element of Dnmt1. Then, the downregulation of Dnmt1 expression level and enzyme activity by mouse Oct4 were further confirmed by transfecting Oct4 siRNA into mouse CCE cells. Our results indicate that the function of Oct4 is involved in DNA methylation by regulating Dnmt1 transcription, especially during the early stages of mouse preimplantation embryo development.