期刊
EPIGENETICS
卷 11, 期 1, 页码 24-35出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15592294.2015.1127479
关键词
epigenetics; cerebellum; SNP; genomic imprinting; Allele-specific DNA methylation; cortex; brain; blood
资金
- UK Medical Research Council (MRC) [MR/K013807/1]
- US National Institutes of Health [AG036039]
- EU-FP7 project EpiTrain (REA) [316758]
- MRC [G1100695, MR/K013807/1, G9318379, MR/L016397/1] Funding Source: UKRI
- Medical Research Council [G9318379, MR/L016397/1, MR/K013807/1, G1100695] Funding Source: researchfish
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 similar to 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: [GRAPHICS] .
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