Oct4 regulates DNA methyltransferase 1 transcription by direct binding of the regulatory element

Fengrui Wu, Qingqing Wu, Dengkun Li, Yuan Zhang, Rong Wang, Yong Liu, Wenyong Li

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