We applied Illumina Human Methylation450K array to perform a genomic-scale 
single-site resolution DNA methylation analysis in neuronal and nonneuronal 
(primarily glial) nuclei separated from the orbitofrontal cortex of postmortem 
human brain. The findings were validated using enhanced reduced representation 
bisulfite sequencing. We identified thousands of sites differentially methylated 
(DM) between neuronal and nonneuronal cells. The DM sites were depleted within 
CpG-island-containing promoters but enriched in predicted enhancers. 
Classification of the DM sites into those undermethylated in neurons (neuronal 
type) and those undermethylated in nonneuronal cells (glial type), combined with 
findings of others that methylation within control elements typically negatively 
correlates with gene expression, yielded large sets of predicted neuron-specific 
and non-neuron-specific genes. These sets of predicted genes were in excellent 
agreement with the available direct measurements of gene expression in human and 
mouse. We also found a distinct set of DNA methylation patterns that were unique 
for neuronal cells. In particular, neuronal-type differential methylation was 
overrepresented in CpG island shores, enriched within gene bodies but not in 
intergenic regions, and preferentially harbored binding motifs for a distinct 
set of transcription factors, including neuron-specific activity-dependent 
factors. Finally, non-CpG methylation was substantially more prevalent in 
neurons than in nonneuronal cells.