低氧诱导因子hif-3α z-bo 2020-10-22 414

　　Hypoxia-inducible factors HIF-1α and HIF-2α are the key regulators of hypoxia stress in cells. So far, the research on their functions has been relatively clear. Under hypoxic conditions, they act as transcription factors that can activate the expression of a series of downstream genes, thereby regulating the response of cells to hypoxia stress. In cells, in addition to HIF-1α and HIF-2α, there is a homologous gene HIF-3α. Because there are multiple transcripts of HIF-3α in cells, the current understanding of its function is relatively lacking, and there are even many conflicting places in existing reports.

　　Cai Xiaolian, Ph.D. from the Fish Hypoxia Biology Group, Institute of Hydrobiology, Chinese Academy of Sciences, etc., conducted a comparative study of fish hypoxia tolerance and sensitivity, and found that fish hif-3α may be closely related to fish response to hypoxia stress. The researchers used CRISPR/Cas9 technology to knock out the hif-3α gene in zebrafish. Under normal culture conditions in the laboratory, there is no significant difference in the development, growth and reproduction of zebrafish lacking hif-3α compared with wild-type zebrafish. However, the number of red blood cells in hif-3α-deficient zebrafish embryos was significantly reduced. In view of the special function of red blood cells to carry oxygen in the body, researchers have systematically compared and analyzed the hypoxic tolerance of zebrafish lacking hif-3α and wild zebrafish. Studies have found that, whether in embryos or adults, the hypoxia tolerance of hif-3α-deficient zebrafish is reduced; the red blood cell development of hif-3α-deficient zebrafish is delayed, most of which are blocked in the initial state, and the number of mature red blood cells is small.

　　"Further analysis found that similar to HIF-1α and HIF-2α, hif-3α also has transcriptional activity and can activate gene expression. Gata1, a key factor regulating red blood cell development, is a direct downstream gene of hif-3α. A series of experiments confirmed that hif-3α can directly bind to the hypoxia response element of the gata1 promoter and activate the expression of gata1, thereby positively regulating the occurrence of red blood cells.