TheHIF1Agene encodes the HIF-1α subunit of hypoxia-inducible factor 1, a transcription factor that is essential for cardiovascular development and systemic O₂homeostasis.HIF1Aconsists of 15 exons that are interrupted by introns at the same locations as in the mouseHif1agene, although sequences mediating alternative splicing and alternative translation initiation events in the mouse are not present in the human gene. Placement of introns differs betweenHIF1AandEPAS1,which encodes the human HIF-2α protein. Transcription of theHIF1Agene was initiated over a 15-nt region downstream of two SP1 sites. A 0.7-kb region of 5′ flanking sequences functioned as a strong promoter in transient expression assays. Comparison of 0.8 kb of 5′ flanking and 5′ untranslated sequences from theHIF1AandHif1agenes revealed 70% identity. The proximal 300 bp of 5′ flanking sequences was 83% identical, including the SP1 sites and transcription initiation sites. These results suggest evolutionary selection for maintenance ofHIF1Astructure, function, and regulation.