| Ethanol-induced methylation of cell cycle genes in neural stem cells. | |
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MedLine Citation:
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PMID: 20626555 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ethanol inhibits the proliferation of neural precursors by altering mitogenic and anti-mitogenic growth factor signaling and can affect global methylation activity in the fetus. We tested the hypothesis that epigenetic modification of specific cell cycle genes underlies the ethanol-induced inhibition of growth factor-regulated cell cycle progression. Monolayer cultures of neural stem cells (NSCs) were treated with fibroblast growth factor 2 or transforming growth factor (TGF) β1 in the absence or presence of ethanol. Ethanol increased the total length of the cell cycle by elongating the amount of time spent in the gap 1 (G1) and synthesis (S) phases of the cell cycle. Ethanol induced the hypermethylation of multiple cell cycle genes associated with the G1/S and gap 2/mitotic phase (G2/M) checkpoints and increased the expression and activity of DNA methyltransferases. These changes were most pronounced in the presence of TGFβ1. Epigenetic alterations paralleled the down-regulation of associated transcripts and other checkpoint-related mRNAs both in vitro (NS-5 cell culture) and in vivo (fetal mouse cortex). Ethanol-induced hypermethylation was accompanied by decreases in the proportion of NSCs expressing associated cell cycle proteins. Thus, ethanol disrupts growth factor-related cell cycle progression by inducing checkpoint restriction at the G1/S transition through a feed-forward system involving the methylation of G2/M regulators. |
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Authors:
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Steven D Hicks; Frank A Middleton; Michael W Miller |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-07-27 |
Journal Detail:
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Title: Journal of neurochemistry Volume: 114 ISSN: 1471-4159 ISO Abbreviation: J. Neurochem. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-24 Completed Date: 2010-10-19 Revised Date: 2011-03-08 |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 1767-80 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry. |
Affiliation:
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Department of Neuroscience and Physiology, State University of New York - Upstate Medical University, Syracuse, NY 13210, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle / drug effects, genetics* Cell Cycle Proteins / biosynthesis*, genetics Cell Line Cell Lineage DNA (Cytosine-5-)-Methyltransferase / biosynthesis DNA Methylation Embryonic Stem Cells / drug effects*, metabolism Epigenesis, Genetic Ethanol / pharmacology* Fibroblast Growth Factor 2 / pharmacology Gene Expression Regulation Humans Kinetics Mice Mice, Inbred C57BL Nerve Tissue / cytology RNA, Messenger / biosynthesis Telencephalon / drug effects, embryology, metabolism Transforming Growth Factor beta1 / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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AA06916/AA/NIAAA NIH HHS; AA07568/AA/NIAAA NIH HHS; AA16151/AA/NIAAA NIH HHS; AA178231/AA/NIAAA NIH HHS; AA18223/AA/NIAAA NIH HHS; R01 AA006916-26/AA/NIAAA NIH HHS; R37 AA007568-20/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/RNA, Messenger; 0/Transforming Growth Factor beta1; 103107-01-3/Fibroblast Growth Factor 2; 64-17-5/Ethanol; EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37/DNA (cytosine-5-)-methyltransferase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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