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<a href="http://doi.org/10.1186/s13148-017-0416-5" target="_blank" rel="noreferrer noopener">http://doi.org/10.1186/s13148-017-0416-5</a>
Pages
117–117
Volume
9
Dublin Core
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Title
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Turnover of histones and histone variants in postnatal rat brain: effects of alcohol exposure.
Publisher
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Clinical epigenetics
Date
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2017
1905-07
Subject
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*2H2O-labeling; *Brain; *Genetic Variation; *Histone; *Mass spectrometry; *Post-translational modifications; *Postnatal alcohol exposure; *Turnover; Acetylation; Animal; Animals; Cell Proliferation; Disease Models; DNA Damage; Epigenesis; Female; Fetal Alcohol Spectrum Disorders/genetics/*metabolism; Genetic; Histones/*genetics/*metabolism; Humans; Post-Translational; Pregnancy; Protein Processing; Proteomics/*methods; Rats; Sprague-Dawley
Creator
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Rachdaoui Nadia; Li Ling; Willard Belinda; Kasumov Takhar; Previs Stephen; Sarkar Dipak
Description
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BACKGROUND: Alcohol consumption during pregnancy is a significant public health problem and can result in a continuum of adverse outcomes to the fetus known as fetal alcohol spectrum disorders (FASD). Subjects with FASD show significant neurological deficits, ranging from microencephaly, neurobehavioral, and mental health problems to poor social adjustment and stress tolerance. Neurons are particularly sensitive to alcohol exposure. The neurotoxic action of alcohol, i.e., through ROS production, induces DNA damage and neuronal cell death by apoptosis. In addition, epigenetics, including DNA methylation, histone posttranslational modifications (PTMs), and non-coding RNA, play an important role in the neuropathology of FASD. However, little is known about the temporal dynamics and kinetics of histones and their PTMs in FASD. RESULTS: We examined the effects of postnatal alcohol exposure (PAE), an animal model of human third-trimester equivalent, on the kinetics of various histone proteins in two distinct brain regions, the frontal cortex, and the hypothalamus, using in vivo (2)H2O-labeling combined with mass spectrometry-based proteomics. We show that histones have long half-lives that are in the order of days. We also show that H3.3 and H2Az histone variants have faster turnovers than canonical histones and that acetylated histones, in general, have a faster turnover than unmodified and methylated histones. Our work is the first to show that PAE induces a differential reduction in turnover rates of histones in both brain regions studied. These alterations in histone turnover were associated with increased DNA damage and decreased cell proliferation in postnatal rat brain. CONCLUSION: Alterations in histone turnover might interfere with histone deposition and chromatin stability, resulting in deregulated cell-specific gene expression and therefore contribute to the development of the neurological disorders associated with FASD. Using in vivo (2)H2O-labeling and mass spectrometry-based proteomics might help in the understanding of histone turnover following alcohol exposure and could be of great importance in enabling researchers to identify novel targets and/or biomarkers for the prevention and management of fetal alcohol spectrum disorders.
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<a href="http://doi.org/10.1186/s13148-017-0416-5" target="_blank" rel="noreferrer noopener">10.1186/s13148-017-0416-5</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*2H2O-labeling
*Brain
*Genetic Variation
*Histone
*Mass spectrometry
*Post-translational modifications
*Postnatal alcohol exposure
*Turnover
2017
Acetylation
Animal
Animals
Cell Proliferation
Clinical epigenetics
Department of Pharmaceutical Sciences
Disease Models
DNA Damage
Epigenesis
Female
Fetal Alcohol Spectrum Disorders/genetics/*metabolism
Genetic
Histones/*genetics/*metabolism
Humans
Kasumov Takhar
Li Ling
NEOMED College of Pharmacy
Post-Translational
Pregnancy
Previs Stephen
Protein Processing
Proteomics/*methods
Rachdaoui Nadia
Rats
Sarkar Dipak
Sprague-Dawley
Willard Belinda