Abstract
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 271 distinct human cell lines were obtained from gene expression omnibus. P-values that describe both miRNA-targeted-gene promoter methylaion 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.Conclusions It was found that promoter methylation was affected by miRNA targeting. Furthermore, miRNA-targeted-gene promoter hypomethylation is suggested to facilitate gene regulation by miRNAs that are not strongly expressed (e.g., miR-548 miRNAs).
Highlights
The epigenetic regulation of gene expression[1] has recently attracted the interests of many researchers
I have taken a number of steps to address any concerns expressed by the reviewers for the first version of this manuscript
Method[21], the promoters of genes that are targets of 70–90% of human miRNAs were significantly hypomethylated, dependent on the statistical tests used, and the definition of promoter methylation levels: the b-value or the amount of methylation. This finding was consistent with conclusions made by Su et al.[11], who stated that miRNAs had a tendency to target genes with hypomethylated promoters
Summary
The epigenetic regulation of gene expression[1] has recently attracted the interests of many researchers. Examples include promoter methylation[2], histone modification[3], the binding of transcription factors to gene promoter regions[4], and miRNA regulation of target genes[5]. Promoter methylation and miRNA regulation of target genes are important in the epigenetic regulation of gene expression. In contrast to DNA methylation, miRNA regulation of target genes is more flexible and can change even during cellular differentiation. MiRNA regulation of target genes and promoter methylation are known to be the primary mechanisms underlying the epigenetic regulation of gene expression. How these two processes cooperatively regulate gene expression has not been extensively studied
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