低氧诱导因子,低氧耐受 z-bo 2020-10-16 298

　　Hypoxia inducers HIF-1α and HIF-2α are important regulators of cells experiencing hypoxia stress. So far, the research on its function is relatively clear. Under hypoxic conditions, they act as transcription factors that can activate the expression of a series of downstream genes, thereby regulating the cell's response to hypoxic stress.

　　"In the cell, in addition to HIF-1α and HIF-2α, there is also a homologous gene HIF-3α. Since HIF-3α has multiple transcripts in cells, the current understanding of its function is relatively poor, and there are even many inconsistencies in existing reports. In a comparative study of fish hypoxic tolerance and sensitivity, Dr. Cai Xiaolian of the Fish Hypoxic Biology Group (including the Institute of Hydrobiology and the Chinese Academy of Sciences) found that fish hif-3α is associated with hypoxia stress The response is closely related. Found that it may be related. The researchers used CRISPR/Cas9 technology to knock out the hif-3α gene in zebrafish.

　　Under normal laboratory culture conditions, compared with wild zebrafish, there is no significant difference in the development, growth and reproduction of zebrafish lacking hif-3α. However, the number of red blood cells in zebrafish embryos lacking hif-3α is significantly reduced. Considering the special function of red blood cells to carry oxygen in the body, the researchers systematically compared and analyzed the hypoxia tolerance of zebrafish lacking hif-3α and wild zebrafish. Studies have shown that zebrafish lacking hif-3α, whether embryonic or adult, have reduced hypoxia tolerance and delayed the development of red blood cells in zebrafish lacking hif-3α, most of which are initially blocked and mature.

　　It is well known that the number of red blood cells is very small. Further analysis showed that hif-3α, like HIF-1α and HIF-2α, has transcriptional activity and can activate gene expression. Gata1 is an important factor regulating red blood cell development, and it 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, activate the expression of gata1, and actively regulate the development of red blood cells.