Vitamin C modulates TET1 function during somatic cell reprogramming
Vitamin C modulates TET1 function during somatic cell reprogramming
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维生素 C 在体细胞重编程过程中调节 TET1 功能
DOI：
10.1038/ng.2807
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发表时间：
2013-12-01
期刊：
影响因子：
30.8
通讯作者：
Pei, Duanqing
中科院分区：
文献类型：
--
作者：
Chen, Jiekai;Guo, Lin;Pei, Duanqing
维生素C是一种以抗人类坏血病活性而闻名的微量营养素，它通过组蛋白去甲基化双加氧酶的活性促进诱导多能干细胞（iPSCs）的产生。TET羟化酶也是参与活性DNA去甲基化的双加氧酶，，，，。在这里，我们报道TET1根据维生素C的缺失或存在，积极或消极地调节体细胞重编程。TET1缺乏会增强重编程，而在维生素C的情况下，TET1的过表达会通过调节间充质到上皮的强制性转化（MET）而损害重编程。在缺乏维生素C的情况下，TET1独立于MET促进体细胞重编程。一致地，TET1以维生素c依赖的方式调节5-羟甲基胞嘧啶（5hmC）在MET关键位点的形成。我们的研究结果表明，维生素C在细胞水平上决定TET1功能的生物学结果中起着至关重要的作用。鉴于其对人类健康的益处，维生素C在表观遗传调节中的作用应进一步研究。
Vitamin C, a micronutrient known for its anti-scurvy activity in humans, promotes the generation of induced pluripotent stem cells (iPSCs) through the activity of histone demethylating dioxygenases,. TET hydroxylases are also dioxygenases implicated in active DNA demethylation,,,,. Here we report that TET1 either positively or negatively regulates somatic cell reprogramming depending on the absence or presence of vitamin C. TET1 deficiency enhances reprogramming, and its overexpression impairs reprogramming in the context of vitamin C,by modulating the obligatory mesenchymal-to-epithelial transition (MET),. In the absence of vitamin C, TET1 promotes somatic cell reprogramming independent of MET. Consistently, TET1 regulates 5-hydroxymethylcytosine (5hmC) formation at loci critical for MET in a vitamin C–dependent fashion. Our findings suggest that vitamin C has a vital role in determining the biological outcome of TET1 function at the cellular level. Given its benefit to human health, vitamin C should be investigated further for its role in epigenetic regulation.