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Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability
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 cing...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348048/ https://www.ncbi.nlm.nih.gov/pubmed/30643296 http://dx.doi.org/10.1038/s41593-018-0297-8 |
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author | Rizzardi, Lindsay F. Hickey, Peter F. DiBlasi, Varenka Rodriguez Tryggvadóttir, Rakel Callahan, Colin M. Idrizi, Adrian Hansen, Kasper D. Feinberg, Andrew P. |
author_facet | Rizzardi, Lindsay F. Hickey, Peter F. DiBlasi, Varenka Rodriguez Tryggvadóttir, Rakel Callahan, Colin M. Idrizi, Adrian Hansen, Kasper D. Feinberg, Andrew P. |
author_sort | Rizzardi, Lindsay F. |
collection | PubMed |
description | 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 CpG and non-CpG differentially methylated regions (CG- and CH-DMRs) only in neuronal cells across regions. While neuronal CH-DMRs were highly associated with differential gene expression, 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, suggesting a mechanistic link between pathology and differential neuron-specific epigenetic regulation in distinct brain regions. |
format | Online Article Text |
id | pubmed-6348048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-63480482019-07-14 Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability Rizzardi, Lindsay F. Hickey, Peter F. DiBlasi, Varenka Rodriguez Tryggvadóttir, Rakel Callahan, Colin M. Idrizi, Adrian Hansen, Kasper D. Feinberg, Andrew P. Nat Neurosci Article 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 CpG and non-CpG differentially methylated regions (CG- and CH-DMRs) only in neuronal cells across regions. While neuronal CH-DMRs were highly associated with differential gene expression, 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, suggesting a mechanistic link between pathology and differential neuron-specific epigenetic regulation in distinct brain regions. 2019-01-14 2019-02 /pmc/articles/PMC6348048/ /pubmed/30643296 http://dx.doi.org/10.1038/s41593-018-0297-8 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Rizzardi, Lindsay F. Hickey, Peter F. DiBlasi, Varenka Rodriguez Tryggvadóttir, Rakel Callahan, Colin M. Idrizi, Adrian Hansen, Kasper D. Feinberg, Andrew P. Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability |
title | Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability |
title_full | Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability |
title_fullStr | Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability |
title_full_unstemmed | Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability |
title_short | Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability |
title_sort | neuronal brain region-specific dna methylation and chromatin accessibility are associated with neuropsychiatric trait heritability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348048/ https://www.ncbi.nlm.nih.gov/pubmed/30643296 http://dx.doi.org/10.1038/s41593-018-0297-8 |
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