Tissue-specific patterns of allelically-skewed DNA methylation.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620276
Title:
Tissue-specific patterns of allelically-skewed DNA methylation.
Authors:
Marzi, S. J.; Meaburn, E. L.; Dempster, E. L.; Lunnon, K.; Paya-Cano, J. L.; Smith, R. G.; Volta, M.; Troakes, C.; Schalkwyk, L. C.; Mill, Jonathan
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.
Citation:
Tissue-specific patterns of allelically-skewed DNA methylation. 2016, 11 (1):24-35 Epigenetics
Publisher:
Taylor & Francis
Journal:
Epigenetics
Issue Date:
Jan-2016
URI:
http://hdl.handle.net/11287/620276
DOI:
10.1080/15592294.2015.1127479
PubMed ID:
26786711
Additional Links:
http://www.tandfonline.com/doi/full/10.1080/15592294.2015.1127479
Type:
Journal Article
Language:
en
ISSN:
1559-2308
Appears in Collections:
Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorMarzi, S. J.en
dc.contributor.authorMeaburn, E. L.en
dc.contributor.authorDempster, E. L.en
dc.contributor.authorLunnon, K.en
dc.contributor.authorPaya-Cano, J. L.en
dc.contributor.authorSmith, R. G.en
dc.contributor.authorVolta, M.en
dc.contributor.authorTroakes, C.en
dc.contributor.authorSchalkwyk, L. C.en
dc.contributor.authorMill, Jonathanen
dc.date.accessioned2017-03-13T10:42:11Z-
dc.date.available2017-03-13T10:42:11Z-
dc.date.issued2016-01-
dc.identifier.citationTissue-specific patterns of allelically-skewed DNA methylation. 2016, 11 (1):24-35 Epigeneticsen
dc.identifier.issn1559-2308-
dc.identifier.pmid26786711-
dc.identifier.doi10.1080/15592294.2015.1127479-
dc.identifier.urihttp://hdl.handle.net/11287/620276-
dc.description.abstractWhile 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.en
dc.language.isoenen
dc.publisherTaylor & Francisen
dc.relation.urlhttp://www.tandfonline.com/doi/full/10.1080/15592294.2015.1127479en
dc.rightsArchived with thanks to Epigeneticsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleTissue-specific patterns of allelically-skewed DNA methylation.en
dc.typeJournal Articleen
dc.identifier.journalEpigeneticsen
dc.type.versionPublisheden

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