Regulation of human erythropoietin gene induction by upstream flanking sequences in transgenic mice.
Regulation of human erythropoietin gene induction by upstream flanking sequences in transgenic mice.
复制标题
转基因小鼠中上游侧翼序列对人促红细胞生成素基因诱导的调节。
DOI：
10.1046/j.1365-2141.1998.01081.x
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发表时间：
1998
影响因子：
6.5
通讯作者：
Madan,A
中科院分区：
文献类型：
--
作者：
Köchling,J;Curtin,PT;Madan,A
Human erythropoietin (Epo) gene expression is inducible by hypoxia or anaemia in the kidney and liver. Previous transgenic mouse experiments have demonstrated that sequences required for Epo gene induction in the kidney reside in a 7.8 kbBam HIfragment located 6 kb upstream of the gene. To sublocalize these sequences, we performed Desoxyribonuclease I (DNAse I) mapping studies using transgenic mice which carried this DNA fragment. These studies revealed a DNAse I hypersensitive site (DNAse I HS) located 4.6 kb from the upstream end of the 7.8 kb fragment in anaemic kidney and liver samples. Sequence analysis of the region encompassing the DNAse I HS revealed an element with remarkable homology to the 3′ Epo gene hypoxia‐inducible enhancer. This suggested the presence of an additional regulatory element that contributes to the control of hypoxia‐inducible Epo gene expression in kidney and liver. We constructed transgenic mice containing the human Epo gene linked to either the 5 kb upstream or 2.5 kb downstream portion of the 7.8 kb fragment. Inducible expression was limited to the liver. Thus, neither fragment was alone sufficient to confer kidney inducible expression. These findings indicate that sequences more than 8.5 kb upstream of the Epo gene are required for kidney‐specific induction. They suggest that either those sequences reside in an 0.3 kbHind IIIfragment located between the 5 kb and the 2.5 kb fragments or that sequences in the 5 kb or 0.3 kb fragments must interact with sequences in the 2.5 kb fragment to allow Epo gene induction in the kidney.
