HYPOXIA-INDUCIBLE NUCLEAR FACTORS BIND TO AN ENHANCER ELEMENT LOCATED 3' TO THE HUMAN ERYTHROPOIETIN GENE

被引:763
|
作者
SEMENZA, GL [1 ]
NEJFELT, MK [1 ]
CHI, SM [1 ]
ANTONARAKIS, SE [1 ]
机构
[1] JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21205 USA
关键词
D O I
10.1073/pnas.88.13.5680
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页码:5680 / 5684
页数:5
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