Premium
An interaction between folate and methylenetetrahydrofolate reductase alters genome‐wide DNA methylation patterns in mouse colon
Author(s) -
Tammen Stephanie Ann,
Park Lara K,
Choi Sang-Woon
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb280
Subject(s) - methylenetetrahydrofolate reductase , dna methylation , methylation , cpg site , microbiology and biotechnology , dna , biology , genomic dna , genetics , gene , chemistry , gene expression , genotype
A common polymorphism at nucleotide 677 of the methylenetetrahydrofolate reductase (MTHFR) gene interacts with folate intake to alter genomic DNA methylation and the risk for colon cancer. We investigated the effects of reduced MTHFR and folate intake on genome‐wide DNA methylation patterns using an intestine specific MTHFR homozygous knockout (KO) mouse model fed 0 or 2ppm folate. DNA was extracted from colonic scrapings, immunoprecipitated with an anti‐5‐methlycytosine antibody and co‐hybridized with input DNA onto a DNA methylation array chip containing probes for all promoters and CpG islands. Probes with a p‐value < 0.01 and mean difference between groups > 0.5 were considered differentially methylated (DM). The contrasts of wild type and KO groups of mice fed either 0 or 2ppm folate yielded 5,613 and 6,360 DM probes respectively. Fewer DM probes (3,328) were found when analyzing the effect of folate intake in KO mice. Applying a two‐way ANOVA for MTHFR and folate interaction yields 3,161 DM probes. We conclude that MTHFR activity has more of an effect on DNA methylation patterns than folate intake. Overall, the MTHFR‐folate interaction plays a significant role in DNA methylation patterns.