June 1995 | GUANG L. WANG, BING-HUA JIANG, ELIZABETH A. RUE, AND GREGG L. SEMENZA*
Hypoxia-inducible factor 1 (HIF-1) is a basic-helix-loop-helix-PAS heterodimer regulated by cellular oxygen tension. This study identifies HIF-1 as a transcription factor essential for hypoxic gene expression, particularly in the erythropoietin gene enhancer. HIF-1 consists of two subunits, HIF-1α and HIF-1β (ARNT), which form a heterodimer. HIF-1α is most closely related to the Drosophila Sim protein, while HIF-1β is a series of ARNT gene products that can heterodimerize with either HIF-1α or AHR. Both subunits are regulated by cellular oxygen tension, with their RNA and protein levels increasing under hypoxic conditions and rapidly decreasing upon reoxygenation. HIF-1 plays a key role in mediating transcriptional responses to hypoxia, including the induction of erythropoietin, vascular endothelial growth factor, and glycolytic enzymes. The study also reveals that HIF-1 is a bHLH-PAS protein, with the PAS domain involved in ligand binding and protein dimerization. The HIF-1α and HIF-1β proteins are expressed in various mammalian cell lines and are involved in hypoxia-inducible transcription. The study further shows that HIF-1 is regulated by both transcriptional and post-transcriptional mechanisms, with its RNA and protein levels tightly controlled by oxygen tension. The results suggest that HIF-1 is a heterodimeric transcription factor that plays a crucial role in mammalian oxygen homeostasis.Hypoxia-inducible factor 1 (HIF-1) is a basic-helix-loop-helix-PAS heterodimer regulated by cellular oxygen tension. This study identifies HIF-1 as a transcription factor essential for hypoxic gene expression, particularly in the erythropoietin gene enhancer. HIF-1 consists of two subunits, HIF-1α and HIF-1β (ARNT), which form a heterodimer. HIF-1α is most closely related to the Drosophila Sim protein, while HIF-1β is a series of ARNT gene products that can heterodimerize with either HIF-1α or AHR. Both subunits are regulated by cellular oxygen tension, with their RNA and protein levels increasing under hypoxic conditions and rapidly decreasing upon reoxygenation. HIF-1 plays a key role in mediating transcriptional responses to hypoxia, including the induction of erythropoietin, vascular endothelial growth factor, and glycolytic enzymes. The study also reveals that HIF-1 is a bHLH-PAS protein, with the PAS domain involved in ligand binding and protein dimerization. The HIF-1α and HIF-1β proteins are expressed in various mammalian cell lines and are involved in hypoxia-inducible transcription. The study further shows that HIF-1 is regulated by both transcriptional and post-transcriptional mechanisms, with its RNA and protein levels tightly controlled by oxygen tension. The results suggest that HIF-1 is a heterodimeric transcription factor that plays a crucial role in mammalian oxygen homeostasis.