Hypoxia inducible factor-1 (HIF-1) directs the cellular response to low oxygen and plays a key role in tumour survival and growth. Here we use an inhibitor of the HIF-1α/HIF-1β protein-protein interaction to show the presence of an epigenetically controlled transactivation loop whereby the HIF-1 transcription factor promotes the expression of its own α-subunit in hypoxic cancer cells.