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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jul 1;88(13):5680–5684. doi: 10.1073/pnas.88.13.5680

Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene.

G L Semenza 1, M K Nejfelt 1, S M Chi 1, S E Antonarakis 1
PMCID: PMC51941  PMID: 2062846

Abstract

Human erythropoietin gene expression in liver and kidney is inducible by anemia or hypoxia. DNase I-hypersensitive sites were identified 3' to the human erythropoietin gene in liver nuclei. A 256-base-pair region of 3' flanking sequence was shown by DNase I protection and electrophoretic mobility-shift assays to bind four or more different nuclear factors, at least two of which are induced by anemia in both liver and kidney, and the region functioned as a hypoxia-inducible enhancer in transient expression assays. These results provide insight into the molecular basis for the regulation of gene expression by a fundamental physiologic stimulus, hypoxia.

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Selected References

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