This cellular response is controlled by the hypoxia-inducible factor (HIF) family of transcription factors, a DNA binding complex that was first defined as a regulator of erythropoietin (Epo) gene (EPO) expression but which is now known to be conserved in all animal species, irrespective of the presence of specialised oxygen transfer systems such as the lungs, heart, and blood (Semenza, 2004).