Alteration of Gene Expression, DNA Methylation, and Histone Methylation in Free Radical Scavenging Networks in Adult Mouse Hippocampus following Fetal Alcohol Exposure.
Alteration of Gene Expression, DNA Methylation, and Histone Methylation in Free Radical Scavenging Networks in Adult Mouse Hippocampus following Fetal Alcohol Exposure.
复制标题
DOI：
10.1371/journal.pone.0154836
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Singh SM
中科院分区：
文献类型：
--
作者：
Chater-Diehl EJ;Laufer BI;Castellani CA;Alberry BL;Singh SM
胎儿酒精谱系障碍(FASD)的分子基础尚不清楚；然而，表观遗传学和基因表达的变化已被牵涉其中。我们已经建立了一种以学习记忆障碍和持续性基因表达变化为特征的FASD小鼠模型。表观遗传标记可能会在老鼠的一生中保持表达的变化，这是一个很少有人探索的领域。在这里，小鼠在出生后第四天和第七天被注射生理盐水或乙醇。在70日龄时，进行基因表达芯片、甲基化DNA免疫沉淀芯片、H3K4me3和H3K27me3染色质免疫沉淀芯片。在对受影响的基因进行广泛的途径分析后，我们确定了受影响最大的基因表达途径是“清除自由基”。我们通过水滴数字聚合酶链式反应证实了其中的6个变化，包括caspase Casp3和Wnt转录因子TCF7L2。所有受甲基化影响的基因的最高途径是“过氧化体生物发生”；我们证实了Acca1硫解酶启动子中存在差异的DNA甲基化。成年海马区氧化应激途径中甲基化和基因表达的改变表明，FASD的表观遗传和氧化应激机制之间存在新的接口。
The molecular basis of Fetal Alcohol Spectrum Disorders (FASD) is poorly understood; however, epigenetic and gene expression changes have been implicated. We have developed a mouse model of FASD characterized by learning and memory impairment and persistent gene expression changes. Epigenetic marks may maintain expression changes over a mouse’s lifetime, an area few have explored. Here, mice were injected with saline or ethanol on postnatal days four and seven. At 70 days of age gene expression microarray, methylated DNA immunoprecipitation microarray, H3K4me3 and H3K27me3 chromatin immunoprecipitation microarray were performed. Following extensive pathway analysis of the affected genes, we identified the top affected gene expression pathway as “Free radical scavenging”. We confirmed six of these changes by droplet digital PCR including the caspase Casp3 and Wnt transcription factor Tcf7l2. The top pathway for all methylation-affected genes was “Peroxisome biogenesis”; we confirmed differential DNA methylation in the Acca1 thiolase promoter. Altered methylation and gene expression in oxidative stress pathways in the adult hippocampus suggests a novel interface between epigenetic and oxidative stress mechanisms in FASD.