Redox-active quinones induces genome-wide DNA methylation changes by an iron-mediated and Tet-dependent mechanism.
Nucleic Acids Res
; 42(3): 1593-605, 2014 Feb.
Article
en En
| MEDLINE
| ID: mdl-24214992
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Quinonas
/
Metilación de ADN
/
Dioxigenasas
/
Hierro
Límite:
Animals
/
Humans
Idioma:
En
Año:
2014
Tipo del documento:
Article