HYPOXIA-INDUCIBLE GENE-EXPRESSION

When oxygen is lacking the cellular production of some hormones, cytokines and glycolytic enzymes can be dramatically increased by a hypoxia-induced increase in the expression of the respective genes that encode for these proteins. The most progress in understanding how the transcription of genes is increased under hypoxic conditions has been made by studying the hypoxia-inducible expression of the erythropoietin gene. Elucidating the oxygen sensitive enhancer elements of the erythropoietin gene has prompted studies on other oxygen-regulated genes. The transcription-regulating proteins that are induced with hypoxia bind to closely related regulatory DNA sequences that control the expression of the genes for erythropoietin, the vascular endothelial growth factor and a number of glycolytic enzymes. It became evident that the hypoxia-inducible enhancer may be part of a widespread oxygen-sensing mechanism acting in a wide variety of mammalian cells. Comparison with the oxygen sensor system in the bacterium Rhizobium meliloti revealed some similarities with the putative oxygen sensor in mammalian cells. This sensor is thought to respond to hypoxia by inducing the signalling cascade that results in binding of the transcription factors to their respective enhancer elements to induce transcription of the respective gene.