Molecular, functional, and gene expression analysis of zebrafish hypoxia-inducible factor-3α

Zhang, P., Lu, L., Yao, Q., Li, Y., Zhou, J., Liu, Y., and Duan, C.
American journal of physiology. Regulatory, integrative and comparative physiology   303(11): R1165-R1174 (Journal)
Registered Authors
Duan, Cunming, Zhou, Jianfeng
HIF, Danio rerio, embryos, oxygen tension, gene expression
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism*
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental/physiology*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Hypoxia
  • Larva/metabolism
  • Molecular Sequence Data
  • Oxygen/metabolism
  • Phylogeny
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Response Elements/physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
23034716 Full text @ Am. J. Physiol. Regul. Integr. Comp. Physiol.

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.

Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes