Abstract
Hypoxia promotes tumor malignancy in solid tumors. One key mechanism by which this occurs is via epigenetic alteration. The present study demonstrates that hypoxia upregulates the expression of the ten-eleven-translocation 5-methylcytosine dioxygenase (TET) enzymes, which catalyze the conversion of 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC), thereby leading to elevated cellular 5-hmC levels in hepatoblastoma HepG2 cells. Hypoxia inducible factor-1α (HIF-1α) is the main transcription factor activated by hypoxia. A chemical inducer of HIF-1α, CoCl2, also increases the expression of TET enzymes. Knockdown of HIF-1α attenuates the hypoxia-induced expression of TET enzymes. These results indicate that hypoxia controls DNA methylation through HIF-1α-mediated TET enzyme regulation in HepG2 cells.