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

Davies, MN and Volta, M and Pidsley, R and Lunnon, K and Dixit, A and Lovestone, S and Coarfa, C and Harris, RA and Milosavljevic, A and Troakes, C and Al-Sarraj, S and Dobson, R and Schalkwyk, LC and Mill, J (2012) 'Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood.' Genome Biology, 13 (6). ISSN 1465-6906

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Abstract

Background: 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.|Results: 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.|Conclusions: 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.

Item Type: Article
Uncontrolled Keywords: Ingenuity Pathway Analysis; Bisulfite Pyrosequencing; Module Eigengene; Methylation Score; Annotate Feature
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 10 Nov 2014 14:43
Last Modified: 23 May 2018 11:15
URI: http://repository.essex.ac.uk/id/eprint/11012

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