biostudies-literatureLupu DSNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSNIEHS NIH HHSNational Institutes of Health2090-2103https://www.ebi.ac.uk/biostudies/studies/S-EPMC5388550biostudies-literatureUnknown31(5)Folate B₁₂-dependent remethylation of homocysteine is important, but less is understood about the importance of the alternative betaine-dependent methylation pathway-catalyzed by betaine-homocysteine methyltransferase (BHMT)-for establishing and maintaining adequate DNA methylation across the genome. We studied C57Bl/6J <i>Bhmt</i> (betaine-homocysteine methyltransferase)-null mice at age 4, 12, 24, and 52 wk (<i>N</i> = 8) and observed elevation of <i>S</i>-adenosylhomocysteine concentrations and development of preneoplastic foci in the liver (increased placental glutathione <i>S</i>-transferase and cytokeratin 8-18 activity; starting at 12 wk). At 4 wk, we identified 63 differentially methylated CpGs (DMCs; false discovery rate < 5%) proximal to 81 genes (across 14 chromosomesFASEB journal : official publication of the Federation of American Societies for Experimental BiologyAltered methylation of specific DNA loci in the liver of <i>Bhmt</i>-null mice results in repression of <i>Iqgap2</i> and <i>F2rl2</i> and is associated with development of preneoplastic foci.PMC5388550DK56350P30 DK056350P30 ES010126Lupu DSPellegrini MOrozco LDCullen JMZeisel SHWang YfalseAltered methylation of specific DNA loci in the liver of <i>Bhmt</i>-null mice results in repression of <i>Iqgap2</i> and <i>F2rl2</i> and is associated with development of preneoplastic foci.Folate B₁₂-dependent remethylation of homocysteine is important, but less is understood about the importance of the alternative betaine-dependent methylation pathway-catalyzed by betaine-homocysteine methyltransferase (BHMT)-for establishing and maintaining adequate DNA methylation across the genome. We studied C57Bl/6J <i>Bhmt</i> (betaine-homocysteine methyltransferase)-null mice at age 4, 12, 24, and 52 wk (<i>N</i> = 8) and observed elevation of <i>S</i>-adenosylhomocysteine concentrations and development of preneoplastic foci in the liver (increased placental glutathione <i>S</i>-transferase and cytokeratin 8-18 activity; starting at 12 wk). At 4 wk, we identified 63 differentially methylated CpGs (DMCs; false discovery rate < 5%) proximal to 81 genes (across 14 chromosomes2017-01-01T00:00:00Z2017 May2026-05-30T07:18:35.422Z2019-03-26T23:33:50ZS-EPMC53885502817942410.1096/fj.201601169R10.1096/fj.201601169r