Possible miRNA coregulation of target genes in brain regions by both differential miRNA expression and miRNA-targeting-specific promoter methylation

Y-h. TaguchiDept. Phys.Chuo Univ.

Introduction

Epigenetic regulation of gene expression is known to be important nowadays.

e.g.

- Development and Cellular Differentiation- Diseases including Cancer - Aging

Example of Epigenetic regulation of genes

- Transcription Factor Bindings to promoter region- Histon modification- Promoter Methylation- miRNA regulation of target genes.

etc. etc.

InteractionRarely Discussed

Both gene suppression

miRNA

cell nucleus

Gene

Promoter3'UTR

Methylation

cytoplasm

Methylation cell nucleus

miRNA cytoplasm

Previous Research

Su et al (2011, BMC Genomics)miRNAs tended to target the geneswith a low DNA methylation level in their promoter regions Promoter methylation miRNA targeting

Purpose of my study:Promoter methylation is miRNA-targeting-specific or not?

(In other words, promoter methylation is affected by being targeted by individual miRNA or not?)

significantly up/downregulated?(t test, Wilcoxon test, KS test)

MiRaGE :MiRNA Ranking by Gene Expression

miRNAtarget gene

target gene

VS

gene

considered miRNA

MiRaGE Method

Promoter Methylation

hypo/hypermethylated?

My Previous Results

Substantial number of miRNAs have target genes with significantly hyper/hypomethylated promoters

References: - Y-h. Taguchi (2012) IPSJ SIG Tech. Rep. 2012-BIO-31(1) pp.1-6- Y-h. Taguchi, (2013) F1000Research [v1; ref status: approved 1, approved with reservations 1, http://f1000r.es/wv]

This Study

Comparison between miRNA, mRNA and promoter methylation among distinct brain regions (Frontal Cortex [FCTX], Temporal Cortex [TCTX], Cerebellum [CRBLM], Pons [PONS]) in miRNA-centric manner.

150 subject vs 4 regions = 600 samples(We exclude samples without all four regions)

Calculation

- Number of miRNAs whose target genes are significantly(*) up/downregulated among 1921 miRNAs

- Number of miRNAs with significantly (*) hypo/hypermethylated promoters among 1921 miRNAs

- Correlation coefficients of mean ranks between miRNA regulation of target genes and miRNA-targeting-specific promoter methylation

for all six pairs of FCTX, TCTX, CRBLM, and PONS

(*) BH adjusted P

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870

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221

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