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

GL Semenza, MK Nejfelt, SM Chi… - Proceedings of the …, 1991 - National Acad Sciences
GL Semenza, MK Nejfelt, SM Chi, SE Antonarakis
Proceedings of the National Academy of Sciences, 1991National Acad Sciences
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 …
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.
National Acad Sciences