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.
Keywords: 5-hydroxymethylcytosine; hypoxia; hypoxia inducible factor-1α; methylation; ten-eleven-translocation 5-methylcytosine dioxygenase.