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SGDP Psychiatric Epigenetics Group Brain Methylome
This site provides access to methylome data generated by the SGDP Psychiatric Epigenetics Group at King's College London

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

Matthew Davies1, Manuela Volta1, Ruth Pidsley1, Katie Lunnon1, Abhishek Dixit1, Simon Lovestone1, Cristian Coarfa2, R. Alan Harris2, Aleksandar Milosavljevic2, Claire Troakes1, Safa Al-Sarraj1, Richard Dobson1, Leonard C. Schalkwyk1, Jonathan Mill1*

1 Institute of Psychiatry, King's College London. UK.
2 Baylor College of Medicine, Houston, Texas. USA.

Genome Biology 2012, 13:R43


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.

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