The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Gene Coexpression Networks in Human Brain Identify Epigenetic Modifications in Alcohol Dependence
Open accessAbstract
Alcohol abuse causes widespread changes in gene expression in human brain, some of which contribute to alcohol dependence. Previous microarray studies identified individual genes as candidates for alcohol phenotypes, but efforts to generate an integrated view of molecular and cellular changes underlying alcohol addiction are lacking. Here, we applied a novel systems approach to transcriptome profiling in postmortem human brains and generated a systemic view of brain alterations associated with alcohol abuse. We identified critical cellular components and previously unrecognized epigenetic determinants of gene coexpression relationships and discovered novel markers of chromatin modifications in alcoholic brain. Higher expression levels of endogenous retroviruses and genes with high GC content in alcoholics were associated with DNA hypomethylation and increased histone H3K4 trimethylation, suggesting a critical role of epigenetic mechanisms in alcohol addiction. Analysis of cell-type-specific transcriptomes revealed remarkable consistency between molecular profiles and cellular abnormalities in alcoholic brain. Based on evidence from this study and others, we generated a systems hypothesis for the central role of chromatin modifications in alcohol dependence that integrates epigenetic regulation of gene expression with pathophysiological and neuroadaptive changes in alcoholic brain. Our results offer implications for epigenetic therapeutics in alcohol and drug addiction.
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Cited by
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Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap
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The Neuroscience of Drug Reward and Addiction
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Canonical genetic signatures of the adult human brain
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Epigenetic mechanisms of drug addiction
Nestler, E. J. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.04.004 · Cited by 454
Metadata
- Authors
- Ponomarev, I., Wang, S., Zhang, L., Harris, R. A., & Mayfield, R. D.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-02-01
- Volume
- 32
- Issue
- 5
- Pages
- 1884-1897
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2082964100
- Cited by
- 383
- References
- 64
- FWCI
- 13.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Ponomarev, I., Wang, S., Zhang, L., Harris, R. A., & Mayfield, R. D. (2012). Gene Coexpression Networks in Human Brain Identify Epigenetic Modifications in Alcohol Dependence. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.3136-11.2012
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