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普遍存在的转录因子OTF-1通过与激素受体的协同相互作用介导MMTV启动子的诱导。

Ubiquitous transcription factor OTF-1 mediates induction of the MMTV promoter through synergistic interaction with hormone receptors.

作者信息

Brüggemeier U, Kalff M, Franke S, Scheidereit C, Beato M

机构信息

Institut für Molekularbiologie und Tumorforschung, Marburg, Federal Republic Germany.

出版信息

Cell. 1991 Feb 8;64(3):565-72. doi: 10.1016/0092-8674(91)90240-y.

DOI:10.1016/0092-8674(91)90240-y
PMID:1846780
Abstract

Steroid hormones induce transcription from the mouse mammary tumor virus (MMTV) promoter by complex mechanisms requiring binding of the hormone receptors to the hormone responsive element (HRE) of the long terminal repeat region. Here we show that the MMTV promoter contains two degenerated octamer motifs immediately upstream of the TATA box that together bind OTF-1 (Oct-1, NFIII) with an affinity similar to the octamer consensus. In transfection experiments, mutation of these octamer motifs interferes with the hormonal response of the MMTV promoter. In vitro, these mutations do not influence basal transcription but completely abolish the stimulatory effect of purified progesterone receptor. Progesterone receptor and glucocorticoid receptor bound to the HRE facilitate binding of OTF-1 to the two octamer motifs. Thus, OTF-1 is a natural mediator of hormonal induction of the MMTV promoter and acts through cooperation with the hormone receptors for binding to DNA.

摘要

类固醇激素通过复杂机制诱导小鼠乳腺肿瘤病毒(MMTV)启动子转录,该机制需要激素受体与长末端重复区域的激素反应元件(HRE)结合。我们在此表明,MMTV启动子在TATA框上游紧邻处含有两个退化的八聚体基序,它们共同以与八聚体共有序列相似的亲和力结合OTF-1(Oct-1,NFIII)。在转染实验中,这些八聚体基序的突变会干扰MMTV启动子的激素反应。在体外,这些突变不影响基础转录,但完全消除了纯化的孕酮受体的刺激作用。与HRE结合的孕酮受体和糖皮质激素受体促进OTF-1与两个八聚体基序的结合。因此,OTF-

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