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.