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Neuronal brain-region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability
Open accessAbstract
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.
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“However, DNA methylation also enhances gene expression through more complicated mechanisms such as the methylation of CCCTC-binding factor (CTCF) binding sites and/or intronic regions (45–49).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [49]
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Metadata
- Authors
- Rizzardi, L. F., Hickey, P. F., Rodriguez DiBlasi, V., Tryggvadóttir, R., Callahan, C. M., Idrizi, A., Hansen, K. D., & Feinberg, A. P.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Hansen, Kasper D.
- Feinberg, Andrew P.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2019-01-14
- Volume
- 22
- Issue
- 2
- Pages
- 307-316
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC6348048
- OpenAlex
- W2951502983
- Cited by
- 146
- References
- 82
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 15 · 2023: 15 · 2022: 26 · 2021: 21 · 2020: 31 · 2019: 12
- FWCI
- 8.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1s10od016315-01)
- National Institute of Mental Health (U01MH104393)
- National Cancer Institute (U24CA180996)
- National Institute of Allergy and Infectious Diseases (P30AI094189)
- Division of Materials Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- DNA methylation, chromatin accessibility, neuropsychiatric traits, heritability, non-CpG methylation, hippocampus, prefrontal cortex, nucleus accumbens, anterior cingulate cortex, schizophrenia, addictive behavior, neuroticism, differential gene expression, regulatory elements, DNA variants
- MeSH terms
- Neuroticism, Brain, Chromatin, Humans, Neurons, Schizophrenia, Genome, Behavior, Addictive, CpG Islands, DNA Methylation, Epigenesis, Genetic
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