Tet 酶通過(guò)將5-甲基胞嘧啶 (5mC) 轉(zhuǎn)化成5-羥甲基胞嘧啶 (5hmC) 和其他氧化的變體來(lái)調(diào)控DNA甲基化,。在這項(xiàng)研究中，維生素C（與Tets屬于同一家族的酶的一個(gè)輔因子）被發(fā)現(xiàn)是小鼠胚胎干細(xì)胞（這些細(xì)胞一般是在沒(méi)有維生素C的情況下培養(yǎng)的）中Tet活性的一個(gè)直接調(diào)控因子,。將維生素C添加到培養(yǎng)介質(zhì)中導(dǎo)致5hmC含量增加和無(wú)數(shù)基因啟動(dòng)子的去甲基化。重塑的DNA甲基化和基因表達(dá)模式與發(fā)生在早期胚胎內(nèi)細(xì)胞團(tuán)塊中的DNA去甲基化相似。（生物谷Bioon.com）
生物谷推薦英文摘要：
Nature doi: 10.1038/nature12362
Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells
Kathryn Blaschke, Kevin T. Ebata, Mohammad M. Karimi, Jorge A. Zepeda-Martínez, Preeti Goyal, Sahasransu Mahapatra, Angela Tam, Diana J. Laird, Martin Hirst, Anjana Rao, Matthew C. Lorincz & Miguel Ramalho-Santos
DNA methylation is a heritable epigenetic modification involved in gene silencing, imprinting, and the suppression of retrotransposons. Global DNA demethylation occurs in the early embryo and the germ line, and may be mediated by Tet (tenneleventranslocation) enzymes, which convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC)7. Tet enzymes have been studied extensively in mouse embryonic stem (ES) cells, which are generally cultured in the absence of vitamin?C, a potential cofactor for Fe(II) 2-oxoglutarate dioxygenase enzymes such as Tet enzymes. Here we report that addition of vitamin C to mouse ES cells promotes Tet activity, leading to a rapid and global increase in 5hmC. This is followed by DNA demethylation of many gene promoters and upregulation of demethylated germline genes. Tet1 binding is enriched near the transcription start site of genes affected by vitamin C treatment. Importantly, vitamin C, but not other antioxidants, enhances the activity of recombinant Tet1 in a biochemical assay, and the vitamin-C-induced changes in 5hmC and 5mC are entirely suppressed in Tet1 and Tet2 double knockout ES cells. Vitamin C has a stronger effect on regions that gain methylation in cultured ES cells compared to blastocysts, and in vivo are methylated only after implantation. In contrast, imprinted regions and intracisternal A particle retroelements, which are resistant to demethylation in the early embryo, are resistant to vitamin-C-induced DNA demethylation. Collectively, the results of this study establish vitamin?C as a direct regulator of Tet activity and DNA methylation fidelity in ES cells.
