Author:
Devall Matthew,Soanes Darren M.,Smith Adam R.,Dempster Emma L.,Smith Rebecca G.,Burrage Joe,Iatrou Artemis,Hannon Eilis,Troakes Claire,Moore Karen,O’Neill Paul,Al-Sarraj Safa,Schalkwyk Leonard,Mill Jonathan,Weedon Michael,Lunnon Katie
Abstract
BackgroundThere is growing interest in the role of DNA methylation in regulating the transcription of mitochondrial genes, particularly in brain disorders characterized by mitochondrial dysfunction. Here, we present a novel approach to interrogate the mitochondrial DNA methylome at single base resolution using targeted bisulfite sequencing. We applied this method to investigate mitochondrial DNA methylation patterns in post-mortem superior temporal gyrus and cerebellum brain tissue from seven human donors.ResultsWe show that mitochondrial DNA methylation patterns are relatively low but conserved, with peaks in DNA methylation at several sites, such as within the D-LOOP and the genes MT-ND2, MT-ATP6, MT-ND4, MT-ND5 and MT-ND6, predominantly in a non-CpG context. The elevated DNA methylation we observe in the D-LOOP we validate using pyrosequencing. We identify loci that show differential DNA methylation patterns associated with age, sex and brain region. Finally, we replicate previously reported differentially methylated regions between brain regions from a methylated DNA immunoprecipitation sequencing study.ConclusionsWe have annotated patterns of DNA methylation at single base resolution across the mitochondrial genome in human brain samples. Looking to the future this approach could be utilized to investigate the role of mitochondrial epigenetic mechanisms in disorders that display mitochondrial dysfunction.
Funder
Alzheimer’s Research UK
Alzheimer's Association
Alzheimer's Society
Medical Research Council
Wellcome Trust
Biotechnology and Biological Sciences Research Council
Subject
Endocrinology, Diabetes and Metabolism
Cited by
7 articles.
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