Open AccessZebrafish hif-3α modulates erythropoiesis via regulation of gata-1 to facilitate hypoxia tolerance
Author(s) -
Xiaolian Cai,
Ziwen Zhou,
Zhu Jian-guo,
Qian Liao,
Dawei Zhang,
Xing Liu,
Jing Wang,
Gang Ouyang,
Wuhan Xiao
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.185116
Subject(s) - erythropoiesis , biology , zebrafish , transcription factor , hypoxia inducible factors , microbiology and biotechnology , hypoxia (environmental) , gene isoform , hypoxia inducible factor 1 , haematopoiesis , regulation of gene expression , gene , genetics , stem cell , medicine , anemia , chemistry , organic chemistry , oxygen
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 hbbe1. hif-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.