期刊
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 88, 期 2, 页码 113-122出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2003.11.008
关键词
progesterone receptor; ERE; sp1; estrogen receptor; gene expression
资金
- NICHD NIH HHS [T32 HD 07028] Funding Source: Medline
- NIDDK NIH HHS [DK53884] Funding Source: Medline
- NIEHS NIH HHS [T32 ES07326] Funding Source: Medline
The progesterone receptor (PR) gene is regulated by estrogen in normal reproductive tissues and in MCF-7 human breast cancer cells. Although it is generally thought that estrogen responsiveness is mediated by interaction of the ligand-occupied estrogen receptor (ER) with estrogen response elements (EREs) in target genes, the human progesterone receptor (PR) gene lacks a palindromic ERE. Promoter A of the PR gene does, however, contain an ERE half site upstream of two adjacent Sp1 sites from +571 to +595, the +571 ERE/Sp1 site. We have examined the individual contributions of the ERE half site and the two Sp1 sites in regulating estrogen responsiveness. Transient transfection assays demonstrated that both Sp1 sites were critical for estrogen- mediated activation of the PR gene. Interestingly, rather than decreasing transcription, mutations in the ERE half site increased transcription substantially suggesting that this site plays a role in limiting transcription. Chromatin immunoprecipitation assays demonstrated that Sp1 was associated with the +571 ERE/Sp1 site in the endogenous PR gene in the absence and in the presence of estrogen, but that ERalpha was only associated with this region of the PR gene after MCF-7 cells had been treated with estrogen. Our studies provide evidence that effective regulation of transcription through the +571 ERE/Sp1 site requires the binding of ERalpha and Sp1 to their respective cis elements and the appropriate interaction of ERa and Sp1 with other coregulatory proteins and transcription factors. (C) 2004 Elsevier Ltd. All rights reserved.
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