Maternal methyl supplements increase offspring DNA methylation at Axin Fused

Genesis. 2006 Sep;44(9):401-6. doi: 10.1002/dvg.20230.


Transient environmental exposures during mammalian development can permanently alter gene expression and metabolism by influencing the establishment of epigenetic gene regulatory mechanisms. The genomic characteristics that confer such epigenetic plasticity upon specific loci, however, have not been characterized. Methyl donor supplementation of female mice before and during pregnancy permanently increases DNA methylation at the viable yellow agouti (A(vy)) metastable epiallele in the offspring. The current study tested whether another murine metastable epiallele, axin fused (Axin(Fu)), similarly exhibits epigenetic plasticity to maternal diet. We found that methyl donor supplementation of female mice before and during pregnancy increased DNA methylation at Axin(Fu) and thereby reduced by half the incidence of tail kinking in Axin(Fu)/+ offspring. The hypermethylation was tail-specific, suggesting a mid-gestation effect. Our results indicate that stochastic establishment of epigenotype at metastable epialleles is, in general, labile to methyl donor nutrition, and such influences are not limited to early embryonic development.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Axin Protein
  • Betaine / metabolism
  • Body Weight
  • Choline / metabolism
  • CpG Islands
  • DNA Methylation*
  • Diet*
  • Dietary Supplements*
  • Epigenesis, Genetic
  • Female
  • Folic Acid / metabolism
  • Gene Expression Regulation
  • Heterozygote
  • Introns
  • Mice
  • Mice, Inbred C57BL
  • Models, Genetic
  • Polymerase Chain Reaction
  • Pregnancy
  • Random Allocation
  • Repressor Proteins / metabolism*
  • Sulfites / pharmacology
  • Vitamin B 12 / metabolism


  • Axin Protein
  • Repressor Proteins
  • Sulfites
  • Betaine
  • Folic Acid
  • Choline
  • Vitamin B 12