Projects per year
The possibility that alterations in DNA methylation are mechanistic drivers of development, aging and susceptibility to disease is widely acknowledged, but evidence remains patchy or inconclusive. Of particular interest in this regard is the brain, where it has been reported that DNA methylation impacts on neuronal activity, learning and memory, drug addiction and neurodegeneration. Until recently, however, little was known about the ‘landscape’ of the human brain methylome. Here we assay 1.9 million CpGs in each of 43 brain samples representing different individuals and brain regions. The cerebellum was a consistent outlier compared to all other regions, and showed over 16 000 differentially methylated regions (DMRs). Unexpectedly, the sequence characteristics of hypo- and hypermethylated domains in cerebellum were distinct. In contrast, very few DMRs distinguished regions of the cortex, limbic system and brain stem. Inter-individual DMRs were readily detectable in these regions. These results lead to the surprising conclusion that, with the exception of cerebellum, DNA methylation patterns are more homogeneous between different brain regions from the same individual, than they are for a single brain region between different individuals. This finding suggests that DNA sequence composition, not developmental status, is the principal determinant of the human brain DNA methylome.
|Number of pages||13|
|Journal||Nucleic Acids Research|
|Early online date||8 Jan 2015|
|Publication status||Published - 30 Jan 2015|
FingerprintDive into the research topics of 'Inter-individual variability contrasts with regional homogeneity in the human brain DNA methylome'. Together they form a unique fingerprint.
- 2 Finished
Core funding renewal for the Wellcome Trust Centre for Cell Biology
1/10/11 → 30/04/17
Methyl-CpG binding proteins in physiology and disease
1/10/05 → 31/03/11
- School of Biological Sciences - Buchanan Chair of Genetics
- Edinburgh Neuroscience
- Centre for Engineering Biology
Person: Academic: Research Active