期刊
GENESIS
卷 44, 期 9, 页码 401-406出版社
WILEY-LISS
DOI: 10.1002/dvg.20230
关键词
developmental origins; epigenetic; metastable epiallele; nutrition
资金
- NIDDK NIH HHS [5K01DK070007] Funding Source: Medline
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 AxinFu 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.
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