Alteration in methylation pattern of GATA-4 promoter region in vitamin A-deficient offspring's heart
Alteration in methylation pattern of GATA-4 promoter region in vitamin A-deficient offspring's heart
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DOI：
10.1016/j.jnutbio.2012.11.005
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发表时间：
2013-07-01
影响因子：
5.6
通讯作者：
Cai, Wei
中科院分区：
文献类型：
--
作者：
Feng, Yi;Zhao, Ling-Zi;Cai, Wei
表观遗传学可以解释生活方式和疾病风险之间的关系。母体饮食已被证明可以动态改变表观遗传调控，包括影响DNA甲基化状态。本研究旨在验证GATA-4基因甲基化会导致维生素a缺乏后代先天性心脏缺陷的假设。断奶雌性大鼠10只（VAN组）饲喂维生素a含量为4 IU /g的日粮，VAD组20只（VAD组）饲喂不含维生素a的日粮，饲养10周后与正常雄性大鼠交配。VAN组和部分VAD组大鼠仍给予与交配前相同的饮食，而VAD组（VADS组）的其余大鼠转移到妊娠周期添加足够维生素a （10 IU/g饮食）的饮食中。在胚胎第13.5天（E13.5）解剖胚胎心脏，观察心脏发育、GATA-4基因甲基化状态和DNA甲基转移酶（dnmt）的表达。维生素a缺乏组胚胎心脏缺陷发生率高。维生素a缺乏组胚胎GATA-4基因CpG位点高度甲基化，GATA-4 mRNA低表达。DNMT1表达上调，DNMT3a和DNMT3b表达下调。这些发现表明，甲基化异常是维生素a缺乏后代心脏缺陷的关键机制之一。dnmt在这一过程中起着关键作用。(C) 2013爱思唯尔公司版权所有。
Epigenetics might explain correlations between lifestyle and risk of disease. Maternal diet has been shown to dynamically alter epigenetic regulation, including affecting DNA methylation status. This study was designed to test the hypothesis that GATA-4 gene methylation would lead to congenital heart defects in vitamin A-deficient offspring. Ten weaning female rats (VAN group) were fed with a diet which contents 4 IU vitamin A/g diet, while 20 rats (VAD group) were maintained on a diet without vitamin A. After 10 weeks of feeding, all the female rats were mated with normal male rats. The VAN group and a portion of VAD group rats were still given the same diet as before mating, while the rest of the rats from the VAD group (VADS group) were transferred to a diet with enough added vitamin A (10 IU/g diet) for the pregnancy cycle. The embryo hearts were dissected out at embryonic day 13.5 (E13.5) for observation of cardiac development, GATA-4 gene methylation status and the expression of DNA methyltransferases (DNMTs). Embryos from vitamin A-deficient group exhibited a high incidence of cardiac defects. High methylation was present in the CpG loci of GATA-4 gene with a low expression of GATA-4 mRNA from vitamin A-deficient group embryos. Moreover, up-regulation of DNMT1 and down-regulation of DNMT3a and DNMT3b expression were found in this group embryo. These findings show that aberrant methylation is one of key mechanisms to heart defects in vitamin A-deficient offspring. DNMTs play a critical role in this process. (C) 2013 Elsevier Inc. All rights reserved.