1Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation, Fuyang Normal University, Fuyang, China.
2Anhui Province Key Laboratory of Environmental Hormone and Reproduction, Fuyang Normal University, Fuyang, China.
Cell Mol Biol Lett. 2018 Aug 16;23:39. doi: 10.1186/s11658-018-0104-2. eCollection 2018.
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 and 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 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 . The downregulation of Dnmt1 expression and enzyme activity by mouse Oct4 were further confirmed by transfecting siRNA into mouse CCE cells.
Our results indicate that Oct4 is involved in DNA methylation through the regulation of transcription, especially during the early stages of mouse pre-implantation embryo development.
转录因子 Oct4 在小鼠胚胎的着床前发育中起着关键作用。DNA 甲基转移酶 1（Dnmt1）在哺乳动物早期胚胎发育过程中维持 DNA 甲基化的变化。目前尚不清楚 Oct4 在小鼠 DNA 甲基化中的作用。在这项研究中，昆明小白鼠被用作动物模型，以揭示哺乳动物胚胎发育过程中 DNA 甲基化与 Oct4 之间的任何相关性。
我们最初使用实时 PCR 研究了 和 的表达情况。它们在着床前阶段表现出不同的模式。此外，通过启动子测定和 ChIP 分析，我们发现 Oct4 通过直接结合到上游调控元件的 -554 至-294 片段来调节小鼠 NIH/3T3 细胞和 CCE 细胞中 的转录活性。通过将 siRNA 转染到小鼠 CCE 细胞中，进一步证实了小鼠 Oct4 对 Dnmt1 表达和酶活性的下调。
我们的结果表明，Oct4 通过调节 转录参与 DNA 甲基化，特别是在小鼠着床前胚胎发育的早期阶段。
