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

Abstract

Science and Technology Norway Discuss this article AbstractmiRNA regulation of target genes and promoter methylation are Background 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.Gene expression and promoter methylation profiles of 271 distinct Methods 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.Significant changes in promoter methylation were associated with Results 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.It was found that promoter methylation was affected by miRNA Conclusions 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).

Impacts of Pretranscriptional DNA Methylation, Transcriptional Transcription Factor, and Posttranscriptional microRNA Regulations on Protein Evolutionary Rate

“…We also report that the level of promoter methylation and N miR have the greatest influence on protein evolutionary rates, and they have a dependent effect on the rate of mammalian protein evolution. This result supports the previously hypothesized potential reciprocal regulation between these two regulatory factors ( Taguchi 2013a , 2013b ).…”

“…Recent studies reported that promoter methylation and miRNA may coregulate their target genes. Changes in promoter methylation may affect miRNA targeting, suggesting a mutual correlation between miRNA-mediated regulation of target genes and miRNA-targeting-specific promoter methylation in brain ( Taguchi 2013a , 2013b ). Promoter methylation of miRNA-targeted genes has also been suggested to be highly correlated with miRNA seed region features ( Taguchi 2013b ).…”

Apparent microRNA-Target-specific Histone Modification in Mammalian Spermatogenesis

“…10,11 Although MiRaGE was originally invented to infer miRNA regulation of target gene expression from target mRNA expression, it has also been used successfully to infer miRNA regulation of promoter methylation. 2,3 Briefly, MiRaGE first computes the amount of differential mRNA expression/promoter methylation/histone modification of the ith gene at the jth sample, ∆x ij (see below for actual definition). It then computes the differential values to group the genes into two sets: genes targeted by the considered miRNA, or genes not targeted by the considered miRNA but targeted by any other miRNAs.…”

“…Recently, Su et al 1 found that miRNAs more frequently target genes with less methylated promoters. More recently, the author used bioinformatics to identify apparent reciprocal regulation of target genes between promoter methylation and miRNAs, 2,3 which has some support from the evolutionary point of view. 4 Thus, seeking more examples of apparent miRNA regulation of other epigenetic factors will deepen our understanding of the epigenetic regulation of mRNAs.…”