GSE96612
Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability [Bisulfite-Seq]
We analyzed differential methylation (via WGBS) between four distinct human brain regions (NAcc-nucleus accumbens, BA9-dorsolateral prefrontal cortex, BA24-anterior cingulate cortex, and HC-hippocampus) in both sorted nuclei and intact tissues. We isolated neuronal and non-neuronal (glial) nuclei from the same six individuals for each tissue via FACS using the neuronal marker, NeuN. Additionally, we performed WGBS from non-sorted tissues from these same brain regions in a total of 12 individuals (BA9 n = 9; BA24 n = 5; HC n = 6; NAcc n = 7). To complement our DNA methylation analyses, we measured gene expression (RNA-seq) and chromatin accessibility (ATAC-seq) in neuronal and non-neuronal nuclei from the nucleus accumbens and dorsolateral prefrontal cortex from six more individuals. We then performed an integrative analysis to understand how the epigenome contributes to brain region-specific function. Overall design: 72 WGBS libraries were sequenced (from intact tissue (27 libraries) and NeuN+ and NeuN- flow sorted nuclei (45 libraries)) from hippocampus, nucleus accumbens, prefrontal cortex (BA9), and anterior cingulate gyrus (BA24). RNA-seq (20 libraries) and ATAC-seq (23 libraries) data from NeuN+ and NeuN- flow sorted nuclei from the nucleus accumbens and prefrontal cortex (BA9) were also obtained.