Objective To investigate the effects of excessive methionine (Met) on hepatic genome-wide methylated status in rats. Methods Twenty-four Wistar rats were allocated into two groups and were fed AIN-93M diet and 1.0% Met-supplemented AIN-93M diet, respectively, for 6 weeks. Hepatic samples were analyzed by Arraystar Rat 4 × 180K RN4 RefSeq Promoter Microarray for genome-wide methylated status. Microarray data was processed by NimbleScan v2.5 software. GO and PATHWAY analysis was performed by the Database for Annotation, Visualization and Integrated Discovery (DAVID) software. Hepatic mRNA and protein expressions of Ednra, Mrvi1 and Gucy1A3 were further assayed by quantitative PCR analysis and ELISA method, respectively. Results A total of 1,092 differentially methylated promoters were found in rat liver after 1.0% Met supplementation. Genes related to smooth muscle contraction, platelet aggregation, and regulation function of blood pressure were changed potentially in expression by excessive Met exposure. Six down-methylated and 13 up-methylated genes were found in several biological pathways after Met treatment, including Mrvi1, Ednra and Gucy1A3. The DNA methylation status of Mrvi1, Ednra and Gucy1A3 were up-regulated, and the mRNA and protein expressions were decreased after Met treatment. Conclusions Excessive methionine supplementation affects hepatic genomic DNA methylation status; Mrvi1, Ednra and Gucy1A3 which is closely associated with smooth muscle contraction, are targets of methylation modulation induced by excessive methionine exposure.
Key words
methionine /
DNA methylation /
rat live
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