Inducible operation of the erythropoietin 3' enhancer in multiple cell lines: evidence for a widespread oxygen-sensing mechanism.
Adaptive responses to hypoxia occur in many biological systems. A well-characterized example is the hypoxic induction of the synthesis of erythropoietin, a hormone which regulates erythropoiesis and hence blood oxygen content. The restricted expression of the erythropoietin gene in subsets of cells within kidney and liver has suggested that this specific oxygen-sensing mechanism is restricted to specialized cells in those organs. Using transient transfection of reporter genes coupled to a transcriptional enhancer lying 3' to the erythropoietin gene, we show that an oxygen-sensing system similar, or identical, to that controlling erythropoietin expression is wide-spread in mammalian cells. The extensive distribution of this sensing mechanism contrasts with the restricted expression of erythropoietin, suggesting that it mediates other adaptive responses to hypoxia.
Maxwell
P H
PH
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
Pugh
C W
CW
Ratcliffe
P J
PJ
D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D003035:Cobalt / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D004921:Erythropoietin / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009928:Organ Specificity; D010100:Oxygen / Q000502:physiology*; D010957:Plasmids; D015183:Restriction Mapping; D014162:Transfection; D014407:Tumor Cells, Cultured
D004921:Erythropoietin; D003035:Cobalt; D010100:Oxygen