Vitamin C modulates TET1 function during somatic cell reprogramming

J Chen, L Guo, L Zhang, H Wu, J Yang, H Liu, X Wang… - Nature …, 2013 - nature.com
J Chen, L Guo, L Zhang, H Wu, J Yang, H Liu, X Wang, X Hu, T Gu, Z Zhou, J Liu, J Liu…
Nature genetics, 2013nature.com
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 …
Abstract
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.
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