Hypoxia inducible factors 1-3 (HIF1-3) are transcription factors that regulate gene expression in response to hypoxia. Compared
to our extensive understanding of HIF-1 and -2, our knowledge of HIF-3 is limited. In this study, we characterized the zebrafish
hif-3α gene and determined its temporal and spatial expression, physiological regulation, and biological activity. We show
that the chromosomal location, gene structure, and protein structure of zebrafish hif-3α are similar to its mammalian orthologs.
When tagged with EGFP and transfected into cultured cells, zebrafish Hif-3α was localized in the nucleus and stimulated reporter
gene expression in a hypoxia response element-dependent manner. During early development, hif-3α mRNA was detected in all
tissues with higher levels in the head. This expression pattern became more apparent in larvae at the 72, 96, and 120 hpf
stages. In the adult stage, hif-3α mRNA was detected in all examined tissues with the highest levels in the ovary. Hypoxia
treatment increased Hif-3α protein levels in both embryos and adults. Hypoxia also increased hif-3α mRNA expression levels
and this regulation was tissue-specific. Expression of a stabilized form of Hif-1α in zebrafish embryos increased the expression
of igfbp-1a, a Hif-1 target gene, whereas it did not change hif-3α mRNA levels, suggesting that hif-3α is not a Hif-1α target.
These results provide new information about the structural and functional conservation, spatial and temporal expression, and
physiological regulation of hif-3α in a teleost model organism.
