Complex 5' genomic structure of the human prolactin receptor: multiple alternative exons 1 and promoter utilization.

Complex 5' genomic structure of the human prolactin receptor: multiple alternative exons 1 and promoter utilization.
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DOI:
10.1210/endo.143.6.8949
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发表时间:
2002-06
期刊:
影响因子:
4.8
通讯作者:
Zhangzhi Hu;L. Zhuang;Jianping Meng;C. Tsai‐Morris;M. Dufau
Zhangzhi Hu;L. Zhuang;Jianping Meng;C. Tsai‐Morris;M. Dufau
中科院分区:
医学2区
文献类型:
--
作者:
Zhangzhi Hu;L. Zhuang;Jianping Meng;C. Tsai‐Morris;M. Dufau

文献摘要

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催乳素受体(PRLR)的转录受多个启动子控制。在最近证明了人类非编码外显子1 hE 1(N)(hE 1(N1))和通用外显子1 hE 1(3)之后,我们鉴定了它们的启动子并表征了另外四个新的人类外显子1(hE 1(N2-5)),它们在人类组织和乳腺癌细胞中选择性剪接到共同的非编码外显子2。确定了含有这些外显子的基因组区域以及5 '侧翼和内含子序列,并在染色体5 p14 -13中确定了它们的顺序。在先前表征的PRLR外显子1物种hE 1(3)(hPII)和hE 1(N1)(hP(N1))的转录中使用的启动子被发现采用不同的机制来控制hPRLR转录。hPIII需要C/EBP β和Sp1/Sp3来实现基础转录活性,而hP(N1)活性由包含Ets元件和NR半位点的结构域赋予。控制hPRLR在多种组织中转录的复杂启动子控制系统对于研究生理和病理状态下PRLR表达的调节具有重要意义。
Transcription of the prolactin receptor (PRLR) is under the control of multiple promoters. Following the recent demonstration of the human non-coding exon 1, hE1(N) (hE1(N1)) and the generic exon 1 hE1(3), we have identified their promoters and characterized four other novel human exons 1 (hE1(N2-5)) that are alternatively spliced to a common non-coding exon 2 in human tissues and breast cancer cells. Genomic regions containing these exons, and 5'-flanking and intronic sequences, were determined and their order was established in chromosome 5p14-13. Promoters utilized in the transcription of previously characterized PRLR exons 1 species hE1(3) (hPII) and hE1(N1) (hP(N1)) were found to employ distinct mechanisms for controlling hPRLR transcription. hPIII requires C/EBP beta and Sp1/Sp3 for basal transcriptional activity, while hP(N1) activity is conferred by domains containing an Ets element and an NR half-site. The complex promoter control system that governs transcription of the hPRLR in multiple tissues is of relevance for studies on the regulation of PRLR expression in physiological and pathological states.