title: Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts.
abstract: Fetal alcohol syndrome (FAS), presenting with a constellation of neuro-/psychological, craniofacial and cardiac abnormalities, occurs frequently in offspring of women who consume alcohol during pregnancy, with a prevalence of 1-3 per 1000 livebirths. The present study was designed to test the hypothesis that alcohol alters global DNA methylation, and modulates expression of the DNA methyltransferases (DNMTs) and various methyl CpG-binding proteins. Murine embryonic fibroblasts (MEFs), utilized as an in vitro embryonic model system, demonstrated ∼5% reduction in global DNA methylation following exposure to 200mM ethanol. In addition, ethanol induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. Such degradation could be completely rescued by pretreatment of MEF cells with the proteasomal inhibitor, MG-132. These data support a potential epigenetic molecular mechanism underlying the pathogenesis of FAS during mammalian development.
authors: University of Louisville Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, ULSD, University of Louisville, Louisville, KY 40202, USA.
authors: Partha
authors: P
authors: Mukhopadhyay
authors: Francine
authors: F
authors: Rezzoug
authors: Jahanzeb
authors: J
authors: Kaikaus
authors: Robert M
authors: RM
authors: Greene
authors: M Michele
authors: MM
authors: Pisano
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000187:drug effects; D000090205:DNA Methyltransferase 3A; D015254:DNA Modification Methylases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004622:Embryo, Mammalian; D000431:Ethanol / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells
chemical_list: D004268:DNA-Binding Proteins; C000715535:Dnmt3a protein, mouse; D000431:Ethanol; D015254:DNA Modification Methylases; D000090205:DNA Methyltransferase 3A
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