Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts

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• 作者：Partha Mukhopadhyay ; Francine Rezzoug ; Jahanzeb Kaikaus ; Robert M. Greene ; M. Michele Pisano ; ^{pisano@louisville.edu}
• 关键词：Fetal alcohol syndrome ; Alcohol ; Mouse ; Embryo ; Fibroblast ; Proteasome ; Epigenetic ; DNA methylation
• 刊名：Reproductive Toxicology
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：37
• 期：Complete
• 页码：40-48
• 全文大小：667 K

文摘

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 200 mM 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.