Differential methylation of the arsenic (III) methyltransferase promoter according to arsenic exposure.
Differential methylation of the arsenic (III) methyltransferase promoter according to arsenic exposure.
复制标题
DOI：
10.1007/s00204-013-1146-x
复制
发表时间：
2014-02
影响因子：
6.1
通讯作者：
Navas-Acien, Ana
中科院分区：
文献类型：
--
作者：
Gribble, Matthew O.;Tang, Wan-yee;Shang, Yan;Pollak, Jonathan;Umans, Jason G.;Francesconi, Kevin A.;Goessler, Walter;Silbergeld, Ellen K.;Guallar, Eliseo;Cole, Shelley A.;Fallin, M. Daniele;Navas-Acien, Ana
无机砷在体内通过砷（III）甲基转移酶甲基化。砷甲基化被认为在砷相关的表观遗传现象中起作用，包括异常DNA和组蛋白甲基化。然而，目前尚不清楚AS3MT基因的启动子（编码砷（III）甲基转移酶）是否因砷暴露而甲基化差异。在这项研究中，我们根据暴露评估了AS3MT启动子甲基化，通过尿砷排泄评估了48名来自强心脏研究的参与者的分层随机样本，他们在1989-1991年和1998-1999年期间测量了基线尿砷和DNA。在这项研究中，所有数据都来自1989-1991年的访问。我们通过亚硫酸盐测序测量了AS3MT启动子在其48个CpG位点的甲基化。我们比较砷暴露组每个CpG位点的平均甲基化百分比，采用线性回归调整研究中心、年龄和性别。AS3MT启动子的低甲基化区域与较高的砷暴露有关。在体外，砷诱导AS3MT启动子低甲基化，增加人外周血单核细胞AS3MT的表达。这些发现可能表明砷暴露会影响一个主要砷代谢基因的表观遗传调控。
Inorganic arsenic is methylated in the body by arsenic (III) methyltransferase. 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 arsenic (III) methyltransferase, 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 1989–1991 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.
登录
查看更多内容
影响因子：
3.6
作者：
Baccarelli A;Bollati V
通讯作者：
Bollati V
影响因子：
4.1
作者：
Drobna, Zuzana;Naranmandura, Hua;Kubachka, Kevin M.;Edwards, Brenda C.;Herbin-Davis, Karen;Styblo, Miroslav;Chris Le, X.;Creed, John T.;Maeda, Noboyu;Hughes, Michael F.;Thomas, David J.
通讯作者：
Thomas, David J.
影响因子：
5
作者：
Gribble, Matthew O.;Howard, Barbara V.;Navas-Acien, Ana
通讯作者：
Navas-Acien, Ana
影响因子：
3.8
作者：
Chen, Baowei;Arnold, Lora L.;Le, X. Chris
通讯作者：
Le, X. Chris
影响因子：
10.4
作者：
Hall M;Gamble M;Slavkovich V;Liu X;Levy D;Cheng Z;van Geen A;Yunus M;Rahman M;Pilsner JR;Graziano J
通讯作者：
Graziano J