Vitamin B12 deficiency in the brain leads to DNA hypomethylation in the TCblR/CD320 knockout mouse.
Vitamin B12 deficiency in the brain leads to DNA hypomethylation in the TCblR/CD320 knockout mouse.
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DOI：
10.1186/1743-7075-9-41
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发表时间：
2012-05-18
影响因子：
4.5
通讯作者：
Quadros EV
中科院分区：
文献类型：
--
作者：
Fernàndez-Roig S;Lai SC;Murphy MM;Fernandez-Ballart J;Quadros EV
DNA甲基化是一种表观遗传现象，可以通过上调或下调基因表达来调节基因功能。维生素B12和叶酸途径参与S-腺苷甲硫氨酸（通用甲基供体）的产生。在20-24周龄的转钴胺素受体（TCblR/CD 320）敲除（KO）（n = 4）和对照小鼠（n = 4）中测定脑维生素B12浓度和整体DNA甲基化。与对照小鼠相比，TCblR/CD 320 KO小鼠中的中值[IQR]脑维生素B12浓度（pg/mg）为8.59 [0.52] vs 112.42 [33.12]; p < 0.05。与对照小鼠相比，TCblR/CD 320 KO小鼠脑基因组DNA中的总体DNA甲基化水平较低（中位数[IQR]：0.31[0.16] % vs 0.55[0.15] %; p < 0.05）。在TCblR/CD 320 KO小鼠中，脑维生素B12在20周期间急剧下降多达90%。这种减少与大脑中整体DNA甲基化减少40%有关。未来的研究将揭示由于DNA低甲基化的变化导致的基因表达谱的破坏是否会导致维生素B12缺乏症中常见的中枢神经系统病理。
DNA methylation is an epigenetic phenomenon that can modulate gene function by up or downregulation of gene expression. Vitamin B12 and folate pathways are involved in the production of S-Adenosylmethionine, the universal methyl donor. Brain vitamin B12 concentration and global DNA methylation was determined in transcobalamin receptor (TCblR/CD320) knock out (KO) (n = 4) and control mice (n = 4) at 20–24 weeks of age. Median [IQR] brain vitamin B12 concentrations (pg/mg) in TCblR/CD320 KO mice compared with control mice was 8.59 [0.52] vs 112.42 [33.12]; p < 0.05. Global DNA methylation levels in brain genomic DNA were lower in TCblR/CD320 KO compared with control mice (Median [IQR]: 0.31[0.16] % vs 0.55[0.15] %; p < 0.05.). In TCblR/CD320 KO mice, brain vitamin B12 drops precipitously by as much as 90% during a 20 week period. This decrease is associated with a 40% decrease in global DNA methylation in the brain. Future research will reveal whether the disruption in gene expression profiles due to changes in DNA hypomethylation contribute to central nervous system pathologies that are frequently seen in vitamin B12 deficiency.
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DOI：
10.1073/pnas.96.17.9751
发表时间：
1999-08-17
影响因子：
11.1
作者：
Hsu, DW;Lin, MJ;Shen, CKJ
通讯作者：
Shen, CKJ
DOI：
10.1002/bdra.20670
发表时间：
2010-07-01
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
3.7
作者：
YOUNGDAHLTURNER, P;MELLMAN, IS;ROSENBERG, LE
通讯作者：
ROSENBERG, LE
影响因子：
30.8
作者：
Jones, PL;Veenstra, GJC;Wolffe, AP
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Wolffe, AP