Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an City, Shandong Province, China.
The Central Hospital of Taian, Tai'an, Shandong , China.
Physiol Genomics. 2018 Mar 1;50(3):158-168. doi: 10.1152/physiolgenomics.00094.2017. Epub 2018 Jan 12.
Folic acid supplements taken during pregnancy can prevent neural tube defects and other developmental abnormalities. Here, we explored the effects of folate supplementation on gene expression and DNA methylation during C2C12 differentiation. Based on the folic acid concentration, this study comprised three groups: low folate (L), normal folate (N), and high-folate supplement (H). Our analyses revealed that differentiation and the mRNA expression of the gene myogenin in C2C12 cell were enhanced by folic acid; however, the overall methylation percentage in myogenin promoter between different treatment groups was not significantly different ( P > 0.05). The results of MeDIP-chip showed that hundreds of differentially methylated regions (DMRs) were identified between every two groups in both promoter and CpG islands, respectively. Genes with DMRs between N and L groups were mainly enriched in the processes of cell differentiation and cell development, whereas those with DMRs between H and N groups were frequently enriched in cellular process/cycle and cell metabolic processes. In addition, correlation analysis between methylation profile and expression profile revealed that some genes were regulated by methylation status directly. Together, these analyses suggest that folate deficiency and supplementation can influence the differentiation, genome-wide DNA methylation level and the expression of myogenesis-related genes including myogenin in the C2C12 cell line.
孕期服用叶酸补充剂可以预防神经管缺陷和其他发育异常。在这里，我们研究了叶酸补充对 C2C12 分化过程中基因表达和 DNA 甲基化的影响。根据叶酸浓度，本研究分为三组：低叶酸 (L)、正常叶酸 (N) 和高叶酸补充 (H)。我们的分析表明，叶酸能增强 C2C12 细胞的分化和肌生成基因的 mRNA 表达；然而，不同处理组间肌生成基因启动子的整体甲基化百分比没有显著差异 (P > 0.05)。MeDIP-chip 的结果表明，在启动子和 CpG 岛之间，每组之间分别鉴定出数百个差异甲基化区域 (DMR)。在 N 和 L 组之间具有 DMR 的基因主要富集在细胞分化和细胞发育过程中，而在 H 和 N 组之间具有 DMR 的基因则经常富集在细胞过程/周期和细胞代谢过程中。此外，甲基化谱和表达谱之间的相关分析表明，一些基因受甲基化状态的直接调控。总之，这些分析表明，叶酸缺乏和补充可以影响 C2C12 细胞系的分化、全基因组 DNA 甲基化水平以及肌生成相关基因（包括肌生成基因）的表达。
