Abstract
BackgroundEpigenetic 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.ResultsWe 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.ConclusionsThese 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.
Highlights
Epigenetic modifications, such as cytosine methylation in CpG-rich regions, regulate multiple functions in mammalian development
Global DNA methylation patterns of the offspring’s cerebral hemispheres from high maternal folic acid The final DNA methylation map presented in this study represents the summary of three biological replicates [12,13], with each mouse collected from an independent litter
The majority of the CpG island-associated differentially methylated region (DMR) were either intergenic or in introns, whereas 18% to 19% were in exons, and approximately 7% were in promoter regions (Figure 1a, b)
Summary
Epigenetic modifications, such as cytosine methylation in CpG-rich regions, regulate multiple functions in mammalian development. 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. To test the hypothesis that excess FA supplementation could alter the methylation in the brains of offspring, 1 week prior to mating, a group of C57BL/6 J female mice were fed a custom AIN-93G amino acid-based diet (Research Diet, Inc., New Brunswick, NJ, USA), with FA at. To understand the dynamics of DNA methylation, genomic DNA from the cerebral hemispheres of the offspring was isolated at postnatal day 1 segregated by gender, and high-resolution, single-base DNA methylation profiling was performed by using next-generation Illumina (Illumina Inc., San Diego, CA, USA) sequencing (details in the Methods section)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
