Epigenetics & Chromatin | Full text | Single-base resolution of mouse offspring brain methylome reveals epigenome modifications caused by gestational folic acid


Epigenetic modifications, such as cytosine methylation in CpG-rich regions, regulate
multiple functions in mammalian development. Maternal nutrients affecting one-carbon
metabolism during gestation can exert long-term effects on the health of the progeny.
Using C57BL/6 J mice, we investigated whether the amount of ingested maternal folic
acid (FA) during gestation impacted DNA methylation in the offspring’s cerebral hemispheres.
Reduced representation bisulfite sequencing at single-base resolution was performed
to analyze genome-wide DNA methylation profiles.


We identified widespread differences in the methylation patterns of CpG and non-CpG
sites of key developmental genes, including imprinted and candidate autism susceptibility
genes (P <0.05). Such differential methylation of the CpG and non-CpG sites may use different
mechanisms to alter gene expressions. Quantitative real time reverse transcription-polymerase
chain reaction confirmed altered expression of several genes.


These finding demonstrate that high maternal FA during gestation induces substantial
alteration in methylation pattern and gene expression of several genes in the cerebral
hemispheres of the offspring, and such changes may influence the overall development.
Our findings provide a foundation for future studies to explore the influence of gestational
FA on genetic/epigenetic susceptibility to altered development and disease in offspring.
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