Greater variability in neuronal than glial DNA methylation patterns

Iwamoto et al. found this in their recent study, by looking at the post-mortem prefrontal cortex and cerebellum of humans and chimpanzees. They separated nuclei from these regions into neuron and non-neuron (i.e., glia) groups with purities of 95 and 99.9%, respectively, using NeuN as a marker for neurons.

They then used magnetic beads to extract methylated DNA molecules from each of these groups and examined the DNA with a tiling array. By looking at the correlation of tiling array probe replicates within the same group (i.e., either neurons or non-neurons), they were able to tell which group had more variability.

They found that this correlation was lower in neuron samples (average R = 0.850) than in non-neuron samples (average R = 0.875). The effect size is not huge, but it is extremely unlikely to be due to chance (see this for yourself in the histogram in fig 8 if you have access).

This is intriguing, if indirect, evidence that epigenetic patterns have an especially large effect on the function of neurons.

It’d be interesting to see a study take a similar approach but select for specific types of brain cells (with different antibodies) to see if there is still high variation within that one class of cells. This would allow us to distinguish between epigenetic changes due to cell type differentiation and those due to neural activity and experience. Of course, purifying a discrete class of brain cells on the basis of one antibody would likely not be so easy.


Iwamoto K, et al. 2011 Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons. Genome Research doi:10.1101/gr.112755.110.