Zebrafish Hif3α modulates erythropoiesis via regulation of gata1 to facilitate hypoxia tolerance
Zebrafish Hif3α modulates erythropoiesis via regulation of gata1 to facilitate hypoxia tolerance
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斑马鱼 Hif3α 通过调节 gata1 来调节红细胞生成，以促进缺氧耐受性。
DOI：
10.1242/dev.185116
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发表时间：
2020-11-01
期刊：
影响因子：
4.6
通讯作者：
Xiao, Wuhan
中科院分区：
文献类型：
--
作者：
Cai, Xiaolian;Zhou, Ziwen;Xiao, Wuhan
低氧诱导因子1α和2α(HIF1α和HIF2α)是细胞对O-2反应的主要调节因子。除HIF1α和HIF2α外，HIF3α是HIFα家族的另一个成员。尽管一些HIF3α亚型是否具有转录活性或抑制活性的问题仍在争论中，但很明显，HIF3α的全长起转录因子的作用。然而，它在低氧信号转导中的作用在很大程度上还不清楚。在这里，我们发现斑马鱼中HIF3a的缺失降低了对低氧的耐受性。进一步的分析表明，由于HIF3a的破坏阻碍了红细胞的成熟，导致红细胞数量减少。我们发现，在hif3a缺失的斑马鱼中，GATAL的表达下调，包括alas2、band 3、hbae1、hbae3和hbbe1在内的几个造血标志基因也是如此。Hif3α识别位于GATA1启动子中的缺氧反应元件，并直接与启动子结合反式激活GATAL表达。我们的结果提示，HIF3a通过调节GATA1调节红细胞生成而促进耐缺氧。
The hypoxia-inducible factors 1 alpha and 2 alpha (HIF1 alpha and HIF2 alpha) are master regulators of the cellular response to O-2. In addition to HIF1 alpha and HIF2 alpha, HIF3 alpha is another identified member of the HIF alpha family. Even though the question of whether some HIF3 alpha isoforms have transcriptional activity or repressive activity is still under debate, it is evident that the full length of HIF3 alpha acts as a transcription factor. However, its function in hypoxia signaling is largely unknown. Here, we show that loss of hif3a in zebrafish reduced hypoxia tolerance. Further assays indicated that erythrocyte number was decreased because red blood cell maturation was impeded by hif3a disruption. We found that gatal expression was downregulated in hif3a null zebrafish, as were several hematopoietic marker genes, including alas2, band3, hbae1, hbae3 and hbbe1. Hif3 alpha recognized the hypoxia response element located in the promoter of gata1 and directly bound to the promoter to transactivate gatal expression. Our results suggested that hif3a facilities hypoxia tolerance by modulating erythropoiesis via gata1 regulation.