Tissue-specific patterns of allelically-skewed DNA methylation

Epigenetics : Official Journal of the DNA Methylation Society
Sarah J MarziJonathan Mill

Abstract

While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are two well-studied sources of allele-specific methylation (ASM), but recent research has indicated a more complex pattern in which genotypic variation can be associated with allelically-skewed DNA methylation in cis. Given the known heterogeneity of DNA methylation across tissues and cell types we explored inter- and intra-individual variation in ASM across several regions of the human brain and whole blood from multiple individuals. Consistent with previous studies, we find widespread ASM with > 4% of the ∼220,000 loci interrogated showing evidence of allelically-skewed DNA methylation. We identify ASM flanking known imprinted regions, and show that ASM sites are enriched in DNase I hypersensitivity sites and often located in an extended genomic context of intermediate DNA methylation. We also detect examples of genotype-driven ASM, some of which are tissue-specific. These findings contribute to our understanding of the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the...Continue Reading

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Apr 8, 2016·Epigenomics·Xinyi LinJoanna D Holbrook
Mar 30, 2017·Journal of Physiology and Biochemistry·Rodrigo San-CristobalJ Alfredo Martinez
Mar 4, 2017·Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie·Valeska StonawskiAnna Eichler
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Methods Mentioned

BETA
Methylation Array

Software Mentioned

R
AnnotationHub Bioconductor package
GenomicRanges
PMCMR R package
SNPMaP
BiQ Analyzer
ENCODE

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