Intraindividual dynamics of transcriptome and genome-wide stability of DNA methylation.

Ryohei Furukawa,Jiro Hitomi,Yuh Shiwa,Tsuyoshi Hachiya,Kenji Sobue,Kanako Ono,Hideki Ohmomo,Sadafumi Suzuki,Atsushi Shimizu,Mamoru Satoh

doi:10.1038/srep26424

Abstract

Cytosine methylation at CpG dinucleotides is an epigenetic mechanism that affects the gene expression profiles responsible for the functional differences in various cells and tissues. Although gene expression patterns are dynamically altered in response to various stimuli, the intraindividual dynamics of DNA methylation in human cells are yet to be fully understood. Here, we investigated the extent to which DNA methylation contributes to the dynamics of gene expression by collecting 24 blood samples from two individuals over a period of 3 months. Transcriptome and methylome association analyses revealed that only ~2% of dynamic changes in gene expression could be explained by the intraindividual variation of DNA methylation levels in peripheral blood mononuclear cells and purified monocytes. These results showed that DNA methylation levels remain stable for at least several months, suggesting that disease-associated DNA methylation markers are useful for estimating the risk of disease manifestation.

Highlights

An increasing number of reports have identified dynamic switching in DNA methylation
In the peripheral blood mononuclear cells (PBMCs) population, the distribution of p-values was greater than that observed in monocytes, with 30–35% of gene expression being associated with cell-type composition (p < 0.05) (Table 1b, Fig. 3b). In these genes associated with cell-type composition, 2–5% were detected as dynamically expressed genes (Table 1). These results suggested that cell-type composition imparts a great effect on the observed levels of gene expression, in PBMCs, and that cell sorting is effective at reducing this effect
We investigated to what extent DNA methylation contributes to dynamic changes in gene expression by collecting blood samples 24 times from two individuals over a 3-month period

Summary

Introduction

An increasing number of reports have identified dynamic switching in DNA methylation. Acute exercise promotes the expression of exercise-responsive genes in parallel with hypomethylation on their promoters[7]. These findings are inconsistent with the prevailing views on DNA methylation as a stable epigenetic marker and suggest the possibility that baseline methylation levels frequently fluctuate in response to various factors, thereby regulating gene expression. We collected 24 blood specimens from two individuals over the course of 3 months and obtained methylome and transcriptome data from peripheral blood mononuclear cells (PBMCs) and isolated monocytes. Based on these data, we examined the contribution of DNA methylation to the short-term dynamics of gene expression

Methods

Results

Conclusion