Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence

Autor: Marina Guizzetti, David P. Gavin, Joel G. Hashimoto, John C. Crabbe, Kristine M. Wiren
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Protein-Arginine N-Methyltransferases
Time Factors
Health (social science)
Epigenetics in learning and memory
Histone lysine methylation
Prefrontal Cortex
Biology
Toxicology
Methylation
Biochemistry
Article
Gene Expression Regulation
Enzymologic
Chromatin remodeling
Alcohol Withdrawal Seizures
Epigenesis
Genetic
Histones
Mice
03 medical and health sciences
Behavioral Neuroscience
Epigenetics of physical exercise
Animals
Gene Regulatory Networks
Epigenetics
DNA Modification Methylases
Inhalation Exposure
Ethanol
Histone ubiquitination
Alcohol Abstinence
Intracellular Signaling Peptides and Proteins
Ubiquitination
Acetylation
Histone-Lysine N-Methyltransferase
General Medicine
DNA Methylation
Chromatin Assembly and Disassembly
Molecular biology
Chromatin
Cell biology
Alcoholism
Disease Models
Animal
030104 developmental biology
Neurology
Histone methyltransferase
Protein Processing
Post-Translational
Zdroj: Alcohol. 60:83-94
ISSN: 0741-8329
DOI: 10.1016/j.alcohol.2017.01.010
Popis: Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines. We found that chronic vapor exposure to highly intoxicating levels of ethanol alters the expression of several chromatin remodeling genes measured by quantitative PCR array analyses. The identified effects were independent of selected lines, which, however, displayed baseline differences in epigenetic gene expression. We reported dysregulation in the expression of genes involved in histone acetylation, deacetylation, lysine and arginine methylation and ubiquitinationhylation during chronic ethanol exposure and withdrawal, but not after 21 days of abstinence. Ethanol-induced changes are consistent with decreased histone acetylation and with decreased deposition of the permissive ubiquitination mark H2BK120ub, associated with reduced transcription. On the other hand, ethanol-induced changes in the expression of genes involved in histone lysine methylation are consistent with increased transcription. The net result of these modifications on gene expression is likely to depend on the combination of the specific histone tail modifications present at a given time on a given promoter. Since alcohol does not modulate gene expression unidirectionally, it is not surprising that alcohol does not unidirectionally alter chromatin structure toward a closed or open state, as suggested by the results of this study.
Databáze: OpenAIRE
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