Correlation between miRNA-targeted-gene promoter methylation and miRNA regulation of target genes

Background: miRNA regulation of target genes and promoter methylation are known to be the primary mechanisms underlying the epigenetic regulation of gene expression. However, how these two processes cooperatively regulate gene expression has not been extensively studied. Methods: Gene expression and promoter methylation profiles of 270 distinct human cell lines were obtained from Gene Expression Omnibus. P -values that describe both miRNA-targeted-gene promoter methylation and miRNA regulation of target genes were computed using the MiRaGE method proposed recently by the author. Results: Significant changes in promoter methylation were associated with miRNA targeting. It was also found that miRNA-targeted-gene promoter hypomethylation was related to differential target gene expression; the genes with miRNA-targeted-gene promoter hypomethylation were downregulated during cell senescence and upregulated during cellular differentiation. Promoter hypomethylation was especially enhanced for genes targeted by miR-548 miRNAs, which are non-conserved, primate-specific miRNAs that are typically expressed at lower levels than the frequently investigated conserved miRNAs. miRNA-targeted-gene promoter methylation may also be related to the seed region features of miRNA. Conclusions: It was found that promoter methylation was correlated to miRNA targeting. Furthermore, miRNA-targeted-gene promoter hypomethylation was especially enhanced in promoters of genes targeted by miRNAs that are not strongly expressed (e.g., miR-548 miRNAs) and was suggested to be highly related to some seed region features of miRNAs.