The human hypoxia-inducible factor 1α gene: HIF1A structure and evolutionary conservation

Narayan V. Iyer, Sandra W. Leung, Gregg L. Semenza

Research output: Contribution to journalArticle

Abstract

The HIF1A gene encodes the HIF-1α subunit of hypoxia-inducible factor 1, a transcription factor that is essential for cardiovascular development and systemic O2 homeostasis. HIF1A consists of 15 exons that are interrupted by introns at the same locations as in the mouse Hif1a gene, although sequences mediating alternative splicing and alternative translation initiation events in the mouse are not present in the human gene. Placement of introns differs between HIF1A and EPAS1, which encodes the human HIF-2α protein. Transcription of the HIF1A gene 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 the HIF1A and Hif1a genes 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 of HIF1A structure, function, and regulation.

Original languageEnglish (US)
Pages (from-to)159-165
Number of pages7
JournalGenomics
Volume52
Issue number2
DOIs
StatePublished - Sep 1 1998

ASJC Scopus subject areas

  • Genetics

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