Cato A C, Skroch P, Weinmann J, Butkeraitis P, Ponta H
Kernforschungszentrum Karlsruhe, Institut für Genetik und Toxikologie, FRG.
EMBO J. 1988 May;7(5):1403-10. doi: 10.1002/j.1460-2075.1988.tb02957.x.
Glucocorticoids, progestins and androgens all induce the transcription of the mouse mammary tumour virus (MMTV) DNA upon binding of their respective receptors to the hormone response element (HRE). This element is located between -202 and -59 5' upstream of the start of transcription on the MMTV long terminal repeat (LTR) region. The HRE contains four repeats of the hexanucleotide 5'-TGTTCT-3' to which the steroid hormone receptors are thought to bind. To investigate the contribution of the individual receptor-binding sites and neighbouring sequences to the steroid hormone action at the MMTV LTR promoter, we mutated various regions of the HRE and studied their response in transfection experiments. Each of the four receptor-binding sites was found to contribute substantially to the overall induction of transcription by all the various steroid hormones tested. This indicates that each individual receptor-binding site on the HRE is important for maximum hormone response. Additionally, we identified four separate sequences outside the receptor binding sites that differentially modulated the response of the MMTV LTR promoter to various steroids. One of these sequences binds the cellular factor, NFI. Thus the interaction of trans-acting factors with sequences outside the hormone receptor-binding sites controls the hormone response of the MMTV LTR promoter.
糖皮质激素、孕激素和雄激素在各自的受体与激素反应元件（HRE）结合后，均可诱导小鼠乳腺肿瘤病毒（MMTV）DNA的转录。该元件位于MMTV长末端重复序列（LTR）区域转录起始点上游5'端的-202至-59之间。HRE包含六核苷酸5'-TGTTCT-3'的四个重复序列，类固醇激素受体被认为与之结合。为了研究单个受体结合位点和相邻序列对MMTV LTR启动子处类固醇激素作用的贡献，我们对HRE的各个区域进行了突变，并在转染实验中研究了它们的反应。发现四个受体结合位点中的每一个对所测试的所有各种类固醇激素的转录总体诱导都有很大贡献。这表明HRE上的每个单独受体结合位点对于最大激素反应都很重要。此外，我们在受体结合位点之外鉴定出四个单独的序列，它们对MMTV LTR启动子对各种类固醇的反应有不同的调节作用。其中一个序列结合细胞因子NFI。因此，反式作用因子与激素受体结合位点之外的序列之间的相互作用控制着MMTV LTR启动子的激素反应。
