Tissue-specific patterns of allelically-skewed DNA methylation. Issue 1 (2nd January 2016)

• Record Type: Journal Article
• Authors: Marzi, Sarah J.; Meaburn, Emma L.; Dempster, Emma L.; Lunnon, Katie; Paya-Cano, Jose L.; Smith, Rebecca G.; Volta, Manuela; Troakes, Claire; Schalkwyk, Leonard C.; Mill, Jonathan
• Is Part Of: Epigenetics. Volume 11:Issue 1(2016)
• Page Start: 24
• Page End: 35
• Publication Date: 2016-01-02
• Subjects: Allele-specific DNA methylation -- blood -- brain -- cerebellum -- cortex -- epigenetics -- genomic imprinting -- SNP; Epigenesis -- Periodicals; Epigenetica; 572.86505
• DOI: 10.1080/15592294.2015.1127479
• Languages: English
• ISSNs: 1559-2294

Abstract

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 .