Tissue-specific patterns of allelically-skewed DNA methylation
File(s)
Author(s)
Type
Journal Article
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 community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood.
Date Issued
2016-01-02
Date Acceptance
2015-11-25
Citation
Epigenetics, 2016, 11 (1), pp.24-35
ISSN
1559-2294
Publisher
Taylor & Francis
Start Page
24
End Page
35
Journal / Book Title
Epigenetics
Volume
11
Issue
1
Copyright Statement
© Sarah J. Marzi, Emma L. Meaburn, Emma L. Dempster, Katie Lunnon, Jose L. Paya-Cano, Rebecca G. Smith, Manuela Volta, Claire Troakes,
Leonard C. Schalkwyk, and Jonathan Mill
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
Leonard C. Schalkwyk, and Jonathan Mill
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000372742300003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Genetics & Heredity
epigenetics
cerebellum
SNP
genomic imprinting
Allele-specific DNA methylation
cortex
brain
blood
ALLELE-SPECIFIC METHYLATION
EXPRESSION
DIFFERENTIATION
SYNAPTOJANIN
SIGNATURES
BRAIN
GRB10
MAPS
Publication Status
Published
Date Publish Online
2016-01-19