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Nat Neurosci. 2019 Feb;22(2):307-316. doi: 10.1038/s41593-018-0297-8. Epub 2019 Jan 14.

Neuronal brain-region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability.

Author information

1
Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3
Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
4
Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. khansen@jhsph.edu.
5
Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. khansen@jhsph.edu.
6
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. khansen@jhsph.edu.
7
Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. afeinberg@jhu.edu.
8
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. afeinberg@jhu.edu.
9
Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA. afeinberg@jhu.edu.
10
Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. afeinberg@jhu.edu.

Abstract

Epigenetic modifications confer stable transcriptional patterns in the brain, and both normal and abnormal brain function involve specialized brain regions. We examined DNA methylation by whole-genome bisulfite sequencing in neuronal and non-neuronal populations from four brain regions (anterior cingulate gyrus, hippocampus, prefrontal cortex, and nucleus accumbens) as well as chromatin accessibility in the latter two. We find pronounced differences in both CpG and non-CpG methylation (CG-DMRs and CH-DMRs) only in neuronal cells across brain regions. Neuronal CH-DMRs were highly associated with differential gene expression, whereas CG-DMRs were consistent with chromatin accessibility and enriched for regulatory regions. These CG-DMRs comprise ~12 Mb of the genome that is highly enriched for genomic regions associated with heritability of neuropsychiatric traits including addictive behavior, schizophrenia, and neuroticism, thus suggesting a mechanistic link between pathology and differential neuron-specific epigenetic regulation in distinct brain regions.

PMID:
30643296
PMCID:
PMC6348048
[Available on 2019-07-14]
DOI:
10.1038/s41593-018-0297-8

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