Regulation of physiological responses to continuous and intermittent hypoxia by hypoxia-inducible factor 1

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor composed of HIF-1alpha and HIF-1beta subunits that functions as a master regulator of oxygen homeostasis. Oxygen-dependent hydroxylation of HIF-1alpha provides a mechanism that allows changes in oxygenation to be transduced to the nucleus, leading to changes in gene expression. Hypoxia-inducible factor 1 plays critical roles in development, physiology and disease pathogenesis. Analyses of mice that are heterozygous for a null allele at the locus encoding the HIF-1alpha subunit have demonstrated that partial deficiency of HIF-1 is sufficient to impair multiple physiological responses to continuous and intermittent hypoxia.