Genome-wide survey reveals dynamic effects of folate supplement on DNA methylation and gene expression during C2C12 differentiation.

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.