Differential methylation of the arsenic (III) methyltransferase promoter according to arsenic exposure.

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Citation: Archives of Toxicology. 88(2):275-82, 2014 Feb.PMID: 24154821Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., ExtramuralSubject headings: *Arsenic/to [Toxicity] | *Arsenic/ur [Urine] | *DNA Methylation/de [Drug Effects] | *Methyltransferases/ge [Genetics] | *Promoter Regions, Genetic/de [Drug Effects] | Aged | Cohort Studies | CpG Islands | Female | Gene Expression Regulation/de [Drug Effects] | Humans | Leukocytes, Mononuclear/de [Drug Effects] | Male | Methyltransferases/me [Metabolism] | Middle AgedYear: 2014ISSN:
  • 0340-5761
Name of journal: Archives of toxicologyAbstract: Inorganic arsenic is methylated in the body by arsenic (III) methyltransferase (AS3MT). Arsenic methylation is thought to play a role in arsenic-related epigenetic phenomena, including aberrant DNA and histone methylation. However, it is unclear whether the promoter of the AS3MT gene, which codes for AS3MT, is differentially methylated as a function of arsenic exposure. In this study, we evaluated AS3MT promoter methylation according to exposure, assessed by urinary arsenic excretion in a stratified random sample of 48 participants from the Strong Heart Study who had urine arsenic measured at baseline and DNA available from 1989 to 1991 and 1998-1999. For this study, all data are from the 1989-1991 visit. We measured AS3MT promoter methylation at its 48 CpG loci by bisulphite sequencing. We compared mean % methylation at each CpG locus by arsenic exposure group using linear regression adjusted for study centre, age and sex. A hypomethylated region in the AS3MT promoter was associated with higher arsenic exposure. In vitro, arsenic induced AS3MT promoter hypomethylation, and it increased AS3MT expression in human peripheral blood mononuclear cells. These findings may suggest that arsenic exposure influences the epigenetic regulation of a major arsenic metabolism gene.All authors: Cole SA, Fallin MD, Francesconi KA, Goessler W, Gribble MO, Guallar E, Navas-Acien A, Pollak J, Shang Y, Silbergeld EK, Tang WY, Umans JGFiscal year: FY2014Digital Object Identifier: Date added to catalog: 2014-11-11
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Journal Article MedStar Authors Catalog Article 24154821 Available 24154821

Inorganic arsenic is methylated in the body by arsenic (III) methyltransferase (AS3MT). Arsenic methylation is thought to play a role in arsenic-related epigenetic phenomena, including aberrant DNA and histone methylation. However, it is unclear whether the promoter of the AS3MT gene, which codes for AS3MT, is differentially methylated as a function of arsenic exposure. In this study, we evaluated AS3MT promoter methylation according to exposure, assessed by urinary arsenic excretion in a stratified random sample of 48 participants from the Strong Heart Study who had urine arsenic measured at baseline and DNA available from 1989 to 1991 and 1998-1999. For this study, all data are from the 1989-1991 visit. We measured AS3MT promoter methylation at its 48 CpG loci by bisulphite sequencing. We compared mean % methylation at each CpG locus by arsenic exposure group using linear regression adjusted for study centre, age and sex. A hypomethylated region in the AS3MT promoter was associated with higher arsenic exposure. In vitro, arsenic induced AS3MT promoter hypomethylation, and it increased AS3MT expression in human peripheral blood mononuclear cells. These findings may suggest that arsenic exposure influences the epigenetic regulation of a major arsenic metabolism gene.

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