Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites

摘要: 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. identified thousands sites differentially methylated (DM) between cells. DM depleted within CpG-island-containing promoters but enriched predicted enhancers. Classification into those undermethylated neurons (neuronal type) cells (glial type), combined with others that control elements typically negatively correlates gene expression, yielded large sets neuron-specific non-neuron-specific genes. These genes excellent agreement available direct measurements expression mouse. also found distinct set patterns unique for In particular, neuronal-type differential was overrepresented CpG island shores, bodies not intergenic regions, preferentially harbored binding motifs transcription factors, including activity-dependent factors. Finally, non-CpG substantially more prevalent than