Functions as a transcriptional regulator of the adaptive response to hypoxia. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Efficient DNA binding requires dimerization with another bHLH protein. Interacts with Vhl. Cytoplasmic in normoxia, nuclear translocation in response to hypoxia. Ubiquitously expressed in the embryo. By hypoxia. The oxygen-dependent degradation (ODD) domain is required for cytoplasmic localization in normoxia.