New androgen receptor genomic targets show an interaction with the ETS1 transcription factor.

New androgen receptor genomic targets show an interaction with the ETS1 transcription factor.
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新的雄激素受体基因组靶标显示与ETS1转录因子的相互作用。

DOI:
10.1038/sj.embor.7401046
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发表时间:
2007-09
期刊:
影响因子:
7.7
通讯作者:
Mills, Ian G.
Mills, Ian G.
中科院分区:
生物学2区
文献类型:
--
作者:
Massie, Charles E.;Adryan, Boris;Barbosa-Morais, Nuno L.;Lynch, Andy G.;Tran, Maxine G.;Neal, David E.;Mills, Ian G.

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雄激素受体(AR)启动重要的发育和致癌转录途径。已知AR作为同二聚体与15个碱基对的二分回文雄激素反应元件结合;然而,已知很少有直接的AR基因靶点。为了鉴定AR启动子靶标,我们使用染色质免疫沉淀和基因组片段的芯片检测。我们确定了1,532个潜在的AR结合位点,包括以前已知的AR基因靶点。许多新的AR靶基因在前列腺癌中显示出改变的表达。AR结合位点的序列分析表明,超过50%的AR结合位点不包含已建立的15 bp AR结合元件。无偏序列分析显示6-bp的基序,这是显着富集,并直接结合的AR在体外。鸟类成红细胞增多症病毒E26同源物(ETS)转录因子家族的结合序列也高度富集,我们发现了AR和ETS 1在AR启动子靶点的一个子集之间的相互作用。
The androgen receptor (AR) initiates important developmental and oncogenic transcriptional pathways. The AR is known to bind as a homodimer to 15-base pair bipartite palindromic androgen-response elements; however, few direct AR gene targets are known. To identify AR promoter targets, we used chromatin immunoprecipitation with on-chip detection of genomic fragments. We identified 1,532 potential AR-binding sites, including previously known AR gene targets. Many of the new AR target genes show altered expression in prostate cancer. Analysis of sequences underlying AR-binding sites showed that more than 50% of AR-binding sites did not contain the established 15 bp AR-binding element. Unbiased sequence analysis showed 6-bp motifs, which were significantly enriched and were bound directly by the AR in vitro. Binding sequences for the avian erythroblastosis virus E26 homologue (ETS) transcription factor family were also highly enriched, and we uncovered an interaction between the AR and ETS1 at a subset of AR promoter targets.
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