Proceedings of The Physiological Society
King's College London (2011) Proc Physiol Soc 22, PC08
Methylomic Profiling Across Multiple human Brain Regions and Blood to Detect Differentially Methylated Regions (DMRs) and Allele-Specific DNA Methylation (ASM)
M. Volta1, L. Schalkwyk1, E. Meaburn1, C. Troakes1, M. Davies1, J. Mill1
1. SGDP, IOP, King's College London, London, United Kingdom.
There is mounting evidence that epigenetic factors play an important role in neurodegenerative diseases such as Alzheimer’s disease. To date, little is known about normal patterns of DNA methylation across different regions of the human brain, and how these compare to those observed in peripheral tissues such as blood. Creating a reference epigenomic map across brain regions and peripheral tissues represents an important first step in disease-focused studies. We carried out methylated DNA immunoprecipitation combined with next-generation sequencing (MeDIP-seq) using peripheral blood and post-mortem tissue representing eight brain regions from the same three individuals. Using the same samples, we also undertook a genome-wide screen for allele-specific DNA methylation (ASM) across brain regions and peripheral blood. We were able to create a comprehensive map of the brain methylome and identify differentially-methylated regions (DMRs) across tissues. Moreover our ASM investigation revealed numerous examples where allelic patterns of DNA methylation are tissue-specific. Overall, patterns of DNA methylation differ across brain regions, with cortical regions being distinct from cerebellum and blood. Levels of DNA methylation at promoter regions tend to be more strongly correlated across tissues, adding to the growing body of evidence that many tissue-specific DMRs are located outside of classic CpG islands. In addition we also found numerous examples of tissue-specific ASM. These data provide a valuable reference for future epigenetic and genetic studies of dementia and neuropsychiatric disease. Data is available for the research community as part of the NIH Epigenome Atlas.
Where applicable, experiments conform with Society ethical requirements