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Open Access Highly Accessed Research

DNA methylation and transcriptional noise

Iksoo Huh1, Jia Zeng2, Taesung Park1 and Soojin V Yi2*

Author Affiliations

1 Department of Statistics, Bioinformatics and Biostatistics Laboratory, Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 151-742, Korea

2 School of Biology, Institute of Bioengineering and Biosciences, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA, 30332, USA

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Epigenetics & Chromatin 2013, 6:9  doi:10.1186/1756-8935-6-9

Published: 26 April 2013

Abstract

Background

DNA methylation is one of the most phylogenetically widespread epigenetic modifications of genomic DNA. In particular, DNA methylation of transcription units (‘gene bodies’) is highly conserved across diverse taxa. However, the functional role of gene body methylation is not yet fully understood. A long-standing hypothesis posits that gene body methylation reduces transcriptional noise associated with spurious transcription of genes. Despite the plausibility of this hypothesis, an explicit test of this hypothesis has not been performed until now.

Results

Using nucleotide-resolution data on genomic DNA methylation and abundant microarray data, here we investigate the relationship between DNA methylation and transcriptional noise. Transcriptional noise measured from microarrays scales down with expression abundance, confirming findings from single-cell studies. We show that gene body methylation is significantly negatively associated with transcriptional noise when examined in the context of other biological factors.

Conclusions

This finding supports the hypothesis that gene body methylation suppresses transcriptional noise. Heavy methylation of vertebrate genomes may have evolved as a global regulatory mechanism to control for transcriptional noise. In contrast, promoter methylation exhibits positive correlations with the level of transcriptional noise. We hypothesize that methylated promoters tend to undergo more frequent transcriptional bursts than those that avoid DNA methylation.

Keywords:
DNA methylation; Gene expression; Spurious transcription; Transcriptional noise