Correlation between miRNA-targeting-specific promotermethylation and miRNA regulation of target genes

Y-H Taguchi

doi:10.12688/f1000research.2-21.v1

Abstract

Background miRNA regulation of target genes and promoter methylation were 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-targeting-specific promoter methylation and miRNA regulation of target genes were computed with the MiRaGE method proposed recently by the author. Results We found that promoter methylation was miRNA-targeting-specific. In other words, changes in promoter methylation were associated with miRNA binding at target genes. It was also found that miRNA-targeting-specific promoter hypomethylation was related to miRNA regulation; the genes with miRNA-targeting-specific promoter hypomethylation were downregulated during cell senescence and upregulated during cellulardierentiation. Promoter hypomethylation was especially enhanced for genes targeted by miR-548 miRNAs, which are non-conserved, and 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-targeting-specific promoter hypomethylation was 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
This finding was consistent with conclusions made by Su et al.[11], who stated that miRNAs had a tendency to target genes with hypomethyl
To the best of my knowledge, this is the first time that miRNA-targeting-specific promoter methylation in many types of cell lines have been observed (Tables 1 and 2). miRNA-targeting-specific hypomethylation was correlated (Tables 3 and 4) with regulation of miRNA target genes, which had a reciprocal relationship with miRNA expression (Table 5); genes with miRNA-targeting-specific hypomethylated promoters were downregulated during cell senescence and upregulated during differentiation

Summary

Introduction

The epigenetic regulation of gene expression[1] has recently attracted the interests of many researchers. The promoter methylation and the 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 rapidly changing. MiRNA-directed gene regulation is thought to result in subtle changes, it is generally believed that miRNAs are involved in many important biological processes ranging from cell division to aging. MiRNA regulation of target genes and promoter methylation were 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

Methods

Results

Conclusion