PUBLICATION

Zebrafish hif-3α modulates erythropoiesis via regulation of gata-1 to facilitate hypoxia tolerance

Authors
Cai, X., Zhou, Z., Zhu, J., Liao, Q., Zhang, D., Liu, X., Wang, J., Ouyang, G., Xiao, W.
ID
ZDB-PUB-201011-9
Date
2020
Source
Development (Cambridge, England)   147(22): (Journal)
Registered Authors
Keywords
Erythropoiesis, Gata-1, Hif-3α, Hypoxia, Zebrafish
MeSH Terms
  • Animals
  • Antigens, Differentiation/biosynthesis
  • Antigens, Differentiation/genetics
  • Apoptosis Regulatory Proteins/genetics
  • Apoptosis Regulatory Proteins/metabolism*
  • Down-Regulation
  • Erythrocytes/metabolism*
  • Erythrocytes/pathology
  • Erythropoiesis*
  • GATA1 Transcription Factor/genetics
  • GATA1 Transcription Factor/metabolism*
  • Hypoxia/genetics
  • Hypoxia/metabolism*
  • Hypoxia/pathology
  • Response Elements
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
33037038 Full text @ Development
Abstract
The hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) are master regulators of the cellular response to O2. In addition to HIF-1α and HIF-2α, HIF-3α is another identified member of the HIF-α gene family. Even though whether some HIF-3α isoforms have transcriptional activity or repressive activity is still under debate, it is evident that the full length of HIF-3α acts as a transcription factor. However, its function in hypoxia signaling is largely unknown. Here, we showed that loss of hif-3α in zebrafish reduced hypoxia tolerance. Further assays indicated that erythrocyte number was decreased because red blood cell maturation was impeded by hif-3α disruption. We found that gata-1 expression was downregulated in hif-3α-null zebrafish, as were several hematopoietic marker genes, including alas2, band3, hbae1, hbae3 and hbbe1hif-3α recognized the hypoxia response element (HRE) located in the promoter of gata-1 and directly bound to the promoter to transactivate gata-1 expression. Our results suggested that hif-3α facilities hypoxia tolerance by modulating erythropoiesis via gata-1 regulation.
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Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
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Mapping