The role of the near upstream sequence in hypoxia-induced expression of the erythropoietin gene.
The role of the near upstream sequence in hypoxia-induced expression of the erythropoietin gene.
复制标题
近上游序列在缺氧诱导的促红细胞生成素基因表达中的作用。
DOI：
10.1093/nar/24.23.4768
复制
发表时间：
1996
影响因子：
14.9
通讯作者：
Goldwasser,E
中科院分区：
文献类型：
--
作者：
Gupta,M;Goldwasser,E
促红细胞生成素（epo）基因的转录受组织缺氧的调节。在这项研究中，我们表明，含有117 bp的EPO启动子序列克隆的荧光素酶报告上游的结构，响应缺氧时，转染到人肝癌细胞系，Hep 3B。相对于鼠epo基因转录起始点的序列-61到45（EP 17）由于缺氧而赋予报告基因表达104倍的诱导。EP 17的内部缺失导致缺氧诱导的损失，而不改变117 bp的epo启动子报告构建体的基础表达。突变研究表明，-53、-59、-49至-51和-55至-57位的碱基对于低氧诱导是必不可少的。EP 17序列是epo基因的3′增强子元件发挥最大功能所必需的。凝胶位移和UV交联实验表明，在Hep 3B核提取物中存在两种蛋白质因子，其分子量约为52 kDa和25 kDa，与EP 17结合。在EP 17区域中引入特定突变，消除缺氧诱导，也消除了这些因子中的一种或两种的结合。这些实验证明了EPO启动子近端区域在EPO基因的缺氧诱导中的作用。
Transcription of the erythropoietin (epo) gene is regulated in response to tissue hypoxia. In this study we show that constructs containing 117 bp of the epo promoter sequence cloned upstream of a luciferase reporter, respond to hypoxia when transfected into the human hepatoma cell line, Hep3B. The sequence −61 to −45 (EP17) relative to the transcription start of the murine epo gene imparted an ∼4-fold induction of reporter gene expression due to hypoxia. Internal deletion of EP17 resulted in loss of induction by hypoxia without altering basal expression of the 117 bp epo promoter reporter construct. Mutagenesis studies showed that the bases at positions −53, −59, from −49 to −51 and from −55 to −57 are essential for hypoxic induction. The EP17 sequence is required for the 3′ enhancer element of the epo gene to be maximally functional. Gel shift and UV cross-linking experiments showed the presence in Hep3B nuclear extracts, of two protein factors with approximate molecular weights of 52 kDa and 25 kDa that bind to EP17. Introduction of specific mutations in the EP17 region that abolish induction by hypoxia, also eliminated the binding of one or both of these factors. These experiments demonstrate a role for the proximal region of the epo promoter in hypoxic induction of the epo gene.
登录
查看更多内容
DOI：
10.1016/s0021-9258(18)98438-3
发表时间：
1991-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ingrid A Beck;S. Ramirez;R. Weinmann;Jaime Caros
通讯作者：
Ingrid A Beck;S. Ramirez;R. Weinmann;Jaime Caros
DOI：
10.1016/s0021-9258(18)98496-6
发表时间：
1991-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Florini;K. Magri;D. Ewton;P. James;K. Grindstaff;P. Rotwein
通讯作者：
J. Florini;K. Magri;D. Ewton;P. James;K. Grindstaff;P. Rotwein
影响因子：
56.9
作者：
GOLDBERG, MA;DUNNING, SP;BUNN, HF
通讯作者：
BUNN, HF
E-box/M-CAT 混合基序和同源结合蛋白调节大鼠心脏 α-肌球蛋白重链基因的基底肌特异性和 cAMP 诱导表达。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Gupta,MP;Gupta,M;Zak,R
通讯作者：
Zak,R
二聚化的转录调控：乱伦关系的两个方面
影响因子：
64.5
作者：
N. Jones
通讯作者：
N. Jones