Time course gene expression in the one-carbon metabolism network using HepG2 cell line grown in folate-deficient medium
Time course gene expression in the one-carbon metabolism network using HepG2 cell line grown in folate-deficient medium
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DOI：
10.1016/j.jnutbio.2008.04.004
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发表时间：
2009-04-01
影响因子：
5.6
通讯作者：
Gueant, Jean-Louis
中科院分区：
文献类型：
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作者：
Chango, Abalo;Nour, Afif Abdel;Gueant, Jean-Louis
叶酸缺乏下叶酸依赖性一碳代谢（FOCM）相关基因表达的综合观点仍不清楚。在人肝癌 HepG2 细胞系的不同时间点（0、2、4、6、12、24 和 48 小时）评估了 FOCM 网络中涉及的 28 个基因转录表达变化的动态。采用实验和计算相结合的方法来强调细胞叶酸缺乏引起的基因表达变化的特征模式。双变量分析表明，叶酸缺乏（叶酸为 0.3 nmol/L，对照培养基为 2.27 μmol/L）在前 2 小时内表现出快速协调的调节，hRfc1（增加 69%）和 Ahcy（减少 437%）的差异表达。通过时间点的密度分析提供了五个基因（Ahcy、Cth、Gnmt、Mat1A、Mtrr 和 hRfc1）差异表达的证据。通过基因表达时间序列分析证实了 Ahcy、Gnmt、Mat1A 和 Mtrr 的差异表达。我们还发现了 Mtrr 的显着差异表达。基因的定性分析可以识别共表达的四个基因簇。其中两个簇与特定的代谢功能一致，因为它们与参与再甲基化（Mthfr 和 Mtrr）和转甲基化（Dnmt1 和 Dnmt3B）途径的基因相关。研究表明，叶酸状态对 HepG2 细胞中 Mtrr 转录有强烈影响。它还表明叶酸缺乏会产生转录变化，特别涉及与再甲基化和转甲基化途径相关的基因簇。 (C) 2009 Elsevier Inc. 保留所有权利。
The integrated view of the expression of genes involved in folate-dependent one-carbon metabolism (FOCM) under folate deficiency remains unknown. Dynamics of changes in the transcriptional expression of 28 genes involved in the FOCM network were evaluated at different time points (0, 2, 4, 6, 12, 24 and 48 h) in human hepatoma HepG2 cell line. Combined experimental and computational approaches were conducted for emphasizing characteristic patterns in the gene expression changes produced by cellular folate deficiency.Bivariate analysis showed that folate deficiency (0.3 nmol/L of folate vs. 2.27 mu mol/L in control medium) displayed rapid and coordinated regulation during the first 2 h with differential expression for hRfc1 (increased by 69%) and Ahcy (decreased by 437%). Density analysis through the time points gave evidence of differential expression for five genes (Ahcy, Cth, Gnmt, Mat1A, Mtrr and hRfc1). Differential expression of Ahcy, Gnmt, Mat1A and Mtrr was confirmed by time-series analysis gene expression. We also found a marked differential expression of Mtrr. Qualitative analysis of genes allowed identifying four clusters of gene that was coexpressed. Two of these clusters were consistent with specific metabolic functions as they associated genes involved in the remethylation (Mthfr and Mtrr) and in the transmethylation (Dnmt1 and Dnmt3B) pathways.The study shows a strong influence of folate status on Mtrr transcription in HepG2 cells. It suggests also that folate deficiency produces transcription changes that particularly involve the clusters of genes related with the remethylation and the transmethylation pathways. (C) 2009 Elsevier Inc. All rights reserved.