Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene.
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.
Semenza
G L
GL
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Nejfelt
M K
MK
Chi
S M
SM
Antonarakis
S E
SE
D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000502:physiology; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000502:physiology; D003850:Deoxyribonuclease I / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D004921:Erythropoietin / Q000235:genetics*; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004921:Erythropoietin; D003850:Deoxyribonuclease I