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人催乳素受体复杂的5'基因组结构:多个可变外显子1及启动子的利用

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

作者信息

Hu Zhang-Zhi, Zhuang Li, Meng Jianping, Tsai-Morris Chon-Hwa, Dufau Maria L

机构信息

Section on Molecular Endocrinology, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Endocrinology. 2002 Jun;143(6):2139-42. doi: 10.1210/endo.143.6.8949.

DOI:10.1210/endo.143.6.8949
PMID:12021177
Abstract

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.

摘要

催乳素受体(PRLR)的转录受多个启动子的控制。在最近证实了人类非编码外显子1、hE1(N)(hE1(N1))和通用外显子1 hE1(3)之后,我们已经鉴定出它们的启动子,并对另外四个新的人类外显子1(hE1(N2 - 5))进行了表征,这些外显子在人类组织和乳腺癌细胞中可选择性剪接至一个共同的非编码外显子2。确定了包含这些外显子以及5'侧翼和内含子序列的基因组区域,并确定了它们在5号染色体p14 - 13上的顺序。发现先前表征的PRLR外显子1物种hE1(3)(hPII)和hE1(N1)(hP(N1))转录中使用的启动子采用不同的机制来控制hPRLR转录。hPIII的基础转录活性需要C/EBPβ和Sp1/Sp3,而hP(N1)的活性由含有Ets元件和NR半位点的结构域赋予。在多个组织中控制hPRLR转录的复杂启动子控制系统与研究PRLR在生理和病理状态下的表达调控相关。

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