Tissue-specific patterns of allelically-skewed DNA methylation

TY - JOUR

T1 - Tissue-specific patterns of allelically-skewed DNA methylation

AU - Marzi, Sarah

AU - Meaburn, Emma Louise

AU - Dempster, Emma L.

AU - Lunnon, Katie Sarah

AU - Paya Cano, Jose Luis

AU - Smith, Rebecca Georgina

AU - Volta, Manuela

AU - Troakes, Claire

AU - Schalkwyk, Leonard Cornelis

AU - Mill, Jonathan

PY - 2016/1/19

Y1 - 2016/1/19

N2 - 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 also tissue-specific. These findings contribute to our understanding about the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood.

AB - 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 also tissue-specific. These findings contribute to our understanding about the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood.

KW - Allele-specific DNA methylation

KW - genomic imprinting

KW - epigenetics

KW - SNP

KW - brain

KW - blood

KW - cerebellum

KW - cortex

U2 - 10.1080/15592294.2015.1127479

DO - 10.1080/15592294.2015.1127479

M3 - Article

SN - 1559-2294

VL - 11

SP - 24

EP - 35

JO - Epigenetics : official journal of the DNA Methylation Society

JF - Epigenetics : official journal of the DNA Methylation Society

IS - 1

ER -