Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1-carbon metabolism.
Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1-carbon metabolism.
复制标题
怀孕期间叶酸摄入量对 IGF2/H19 基因组印记和 1-碳代谢的影响。
DOI：
10.1096/fj.201601214rr
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Michels,KarinB
中科院分区：
文献类型：
--
作者：
Tserga,Aggeliki;Binder,AlexandraM;Michels,KarinB
叶酸是1-碳代谢的重要组成部分，它产生DNA甲基化的甲基。基因组印记的破坏导致双等位基因表达，这可能会影响疾病易感性，可能反映在高水平的S-腺苷-高半胱氨酸（SAH）和低水平的S-腺苷-甲硫氨酸（SAM）上。我们调查了90个母亲-儿童二对儿的胎盘和脐带血中IGF 2和H19基因的印迹（LOI）缺失与妊娠期间叶酸补充剂之间的关联，并与亚甲基四氢叶酸还原酶（MTHFR）基因型相关。使用焦磷酸测序来评估47个H19杂合胎盘和37个胎盘以及48个胎盘的IGF 2和H19甲基化水平杂合的脐带血组织中单等位基因表达的偏差。我们检测到松弛印记（ROI）和LOI的H19在胎盘中不相关的差异甲基化水平的H19 ICR。胎盘保留了IGF 2的单等位基因特异性基因表达，但32.4%的脐带血样本显示IGF 2的LOI，10.8%显示ROI。高SAH水平与低H19甲基化显著相关。在B12水平低的婴儿中，SAM/SAH比值与H19甲基化水平高之间存在有趣的正相关。我们的数据表明，胎盘和脐带血中印记的调节存在深刻的差异;甲基化组，转录组和蛋白质组缺乏相关性;以及出生时游离甲基和基因组印记之间复杂的调节反馈网络。Tserga，A.，Binder，A. M.，Michels，K. B。孕期叶酸摄入对IGF 2/H19基因组印记和1-碳代谢的影响
Folic acid is an essential component of 1-carbon metabolism, which generates methyl groups for DNA methylation. Disruption of genomic imprinting leads to biallelic expression which may affect disease susceptibility possibly reflected in high levels of S-adenosyl-homocysteine (SAH) and low levels of S-adenosyl-methionine (SAM). We investigated the association between folic acid supplementation during pregnancy and loss of imprinting (LOI) of IGF2 and H19 genes in placentas and cord blood of 90 mother–child dyads in association with the methylenetetrahydrofolate reductase (MTHFR) genotype. Pyrosequencing was used to evaluate deviation from monoallelic expression among 47 placentas heterozygous for H19 and 37 placentas and cord blood tissues heterozygous for IGF2 and H19 methylation levels of 48 placentas. We detected relaxation of imprinting (ROI) and LOI of H19 in placentas not associated with differences in methylation levels of the H19ICR. Placentas retained monoallelic allele-specific gene expression of IGF2, but 32.4% of cord blood samples displayed LOI of IGF2 and 10.8% showed ROI. High SAH levels were significantly associated with low H19 methylation. An interesting positive association between SAM/SAH ratio and high H19 methylation levels was detected among infants with low B12 levels. Our data suggest profound differences in regulation of imprinting in placenta and cord blood; a lack of correlation of the methylome, transcriptome, and proteome; and a complex regulatory feedback network between free methyl groups and genomic imprinting at birth.—Tserga, A., Binder, A. M., Michels, K. B. Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1-carbon metabolism.