Health & Environmental Research Online (HERO)


Print Feedback Export to File
4351272 
Journal Article 
Redox-active quinones induces genome-wide DNA methylation changes by an iron-mediated and Tet-dependent mechanism 
Zhao, B; Yang, Y; Wang, X; Chong, Z; Yin, R; Song, SH; Zhao, C; Li, C; Huang, H; Sun, BF; Wu, D; Jin, KX; Song, M; Zhu, BZ; Jiang, G; Rendtlew Danielsen, JM; Xu, GL; Yang, YG; Wang, H 
2014 
1 
Nucleic Acids Research
ISSN: 0305-1048
EISSN: 1362-4962 
42 
3 
1593-1605 
English 
24214992 
WOS:000331138800021 
DNA methylation has been proven to be a critical epigenetic mark important for various cellular processes. Here, we report that redox-active quinones, a ubiquitous class of chemicals found in natural products, cancer therapeutics and environment, stimulate the conversion of 5 mC to 5 hmC in vivo, and increase 5 hmC in 5751 genes in cells. 5 hmC increase is associated with significantly altered gene expression of 3414 genes. Interestingly, in quinone-treated cells, labile iron-sensitive protein ferritin light chain showed a significant increase at both mRNA and protein levels indicating a role of iron regulation in stimulating Tet-mediated 5 mC oxidation. Consistently, the deprivation of cellular labile iron using specific chelator blocked the 5 hmC increase, and a delivery of labile iron increased the 5 hmC level. Moreover, both Tet1/Tet2 knockout and dimethyloxalylglycine-induced Tet inhibition diminished the 5 hmC increase. These results suggest an iron-regulated Tet-dependent DNA demethylation mechanism mediated by redox-active biomolecules.