Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood

By M. Davies, M. Volta, Ruth Pidsley, K. Lunnon, A. Dixit, S. Lovestone, Cristian Coarfa, R. A. Harris, Aleksandar Milosavljevic, C. Troakes and 4 more. Genome Biology, 2012

652 citations recorded by the source corpus.

Dynamic changes to the epigenome play a critical role in establishing and maintaining cellular phenotype during differentiation, but little is known about the normal methylomic differences that occur between functionally distinct areas of the brain. We characterized intra- and inter-individual methylomic variation across whole blood and multiple regions of the brain from multiple donors. Distinct tissue-specific patterns of DNA methylation were identified, with a highly significant over-representation of tissue-specific differentially methylated regions (TS-DMRs) observed at intragenic CpG islands and low CG density promoters. A large proportion of TS-DMRs were located near genes that are differentially expressed across brain regions. TS-DMRs were significantly enriched near genes involved in functional pathways related to neurodevelopment and neuronal differentiation, including BDNF, BMP4, CACNA1A, CACA1AF, EOMES, NGFR, NUMBL, PCDH9, SLIT1, SLITRK1 and SHANK3. Although between-tissue variation in DNA methylation was found to greatly exceed between-individual differences within any one tissue, we found that some inter-individual variation was reflected across brain and blood, indicating that peripheral tissues may have some utility in epidemiological studies of complex neurobiological phenotypes. This study reinforces the importance of DNA methylation in regulating cellular phenotype across tissues, and highlights genomic patterns of epigenetic variation across functionally distinct regions of the brain, providing a resource for the epigenetics and neuroscience research communities.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a191dafa8c38e2a37004261468de68d4bc8732df

How researchers see this paper

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In Genetics

1. Meaghan J. Jones
2. Michael S. Kobor
3. S. Goodman

In Molecular Biology

1. Meaghan J. Jones
2. Michael S. Kobor
3. S. Goodman

Citations in the corpus

• Effects of the social environment and stress on glucocorticoid receptor gene methylation: a systematic review (2014, neutral): “These findings appear despite the significant evidence of tissue-specific DNA methylation profiles (60-63), leading to the question of how a ‘social adversity-related’ epigenetic signal might appear in cell populations as diverse as peripheral blood cells and CNSderived cells.”
• DNA methylation and healthy human aging (2015, background): “…Sarah J. Goodman1,2 and Michael S. Kobor1,2,3 1Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, 2Department of Medical Genetics, 3Human Early Learning Partnership, School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada”