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 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.

CB1‐receptor knockout neonatal mice are protected against ethanol‐induced impairments of DNMT1, DNMT3A, and DNA methylation

“…Similar degradation of DNA methyltransferases by ethanol exposure during the embryonic period was observed (Mukhopadhyay et al . ). However, this degradation is mediated through the ubiquitin–proteasome pathways (Mason et al .…”

“…In an embryonic ethanol model, ethanol enhanced the expression of DNMT3A and 3B, but not DNMT1 (Mukhopadhyay et al . ) genes. A recent study reported that ethanol exposure significantly impaired DNA methylation (5‐mC staining) in both the dorsal and the ventral neural tube and that led to developmental delay (Zhou et al .…”

A systematic evaluation of microRNAs in regulating human hepatic CYP2E1

“…The hsa-miR-214-3p mimic or miR-NC was introduced into HepG2 cells by transfection and the cells were incubated overnight. On the following morning, the transfected HepG2 cells were treated with 200 mM ethanol for 24 h prior to harvesting for RNA and protein analyses [26]. …”

Epigenetic Impact of Nutrition

“…The mechanisms described include the degradation of DNA methyltransferases, and methyl binding proteins (MeCP2, Mbd2, and Mbd3) by proteasomal degradation, followed by DNA hypomethylation (Mukhopadhyay et al, 2013). The mechanisms described include the degradation of DNA methyltransferases, and methyl binding proteins (MeCP2, Mbd2, and Mbd3) by proteasomal degradation, followed by DNA hypomethylation (Mukhopadhyay et al, 2013).…”