Single-base Resolution of Mouse Offspring Brain Methylome Reveals Epigenome Modifications Caused by Gestational Folic Acid

Overview

Journal Epigenetics Chromatin

Publisher Biomed Central

Specialties Biochemistry
Genetics

Date 2014 Feb 4

PMID 24484737

Citations 37

Authors

Subit Barua

Salomon Kuizon

Kathryn K Chadman

Michael J Flory

W Ted Brown

Mohammed A Junaid

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

Citing Articles

Risk of Excess Maternal Folic Acid Supplementation in Offspring.

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Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms.

Ondicova M, Irwin R, Thursby S, Hilman L, Caffrey A, Cassidy T Clin Epigenetics. 2022; 14(1):63.

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