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Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation.


ABSTRACT: Transcriptional responses to hypoxia are primarily mediated by hypoxia-inducible factor (HIF), a heterodimer of HIF-alpha and the aryl hydrocarbon receptor nuclear translocator subunits. The HIF-1alpha and HIF-2alpha subunits are structurally similar in their DNA binding and dimerization domains but differ in their transactivation domains, implying they may have unique target genes. Previous studies using Hif-1alpha(-/-) embryonic stem and mouse embryonic fibroblast cells show that loss of HIF-1alpha eliminates all oxygen-regulated transcriptional responses analyzed, suggesting that HIF-2alpha is dispensable for hypoxic gene regulation. In contrast, HIF-2alpha has been shown to regulate some hypoxia-inducible genes in transient transfection assays and during embryonic development in the lu

SUBMITTER: Hu CJ 

PROVIDER: S-EPMC309606 | biostudies-literature | 2003 Dec

REPOSITORIES: biostudies-literature