Abstract:
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 2H2O-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 2H2O-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.
journal_name
Clin Epigeneticsjournal_title
Clinical epigeneticsauthors
Rachdaoui N,Li L,Willard B,Kasumov T,Previs S,Sarkar Ddoi
10.1186/s13148-017-0416-5subject
Has Abstractpub_date
2017-10-23 00:00:00pages
117eissn
1868-7075issn
1868-7083pii
416journal_volume
9pub_type
杂志文章abstract:BACKGROUND:Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic hea...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0558-0
更新日期:2018-10-20 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0421-8
更新日期:2017-11-07 00:00:00
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journal_title:Clinical epigenetics
pub_type: 已发布勘误
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0063-7
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pub_type: 杂志文章
doi:10.1186/s13148-018-0523-y
更新日期:2018-07-05 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章,评审
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journal_title:Clinical epigenetics
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doi:10.1186/s13148-018-0539-3
更新日期:2018-08-06 00:00:00
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pub_type: 杂志文章
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更新日期:2012-01-30 00:00:00
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更新日期:2018-07-13 00:00:00
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journal_title:Clinical epigenetics
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doi:10.1186/s13148-017-0434-3
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doi:10.1186/s13148-020-00844-2
更新日期:2020-04-07 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-021-01017-5
更新日期:2021-01-30 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-5-6
更新日期:2013-04-26 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0445-8
更新日期:2018-01-23 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0567-z
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pub_type: 临床试验,杂志文章
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pub_type: 杂志文章
doi:10.1186/s13148-020-00930-5
更新日期:2020-09-11 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
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更新日期:2017-04-24 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00875-9
更新日期:2020-06-09 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0794-y
更新日期:2019-12-19 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0798-7
更新日期:2020-01-13 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
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更新日期:2016-03-15 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-014-0040-6
更新日期:2015-01-22 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0646-9
更新日期:2019-03-11 00:00:00