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Jun-Fos以及维生素A和D的受体识别出人类骨钙素基因中的一个共同反应元件。

Jun-Fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene.

作者信息

Schüle R, Umesono K, Mangelsdorf D J, Bolado J, Pike J W, Evans R M

机构信息

Howard Hughes Medical Institute, Salk Institute, La Jolla, California 92037.

出版信息

Cell. 1990 May 4;61(3):497-504. doi: 10.1016/0092-8674(90)90531-i.

Abstract

We present evidence that the vitamin D response element in the human osteocalcin gene confers responsiveness to the vitamin A metabolite, retinoic acid. Retinoic acid receptor (RAR) expressed in E. coli binds to this sequence in vitro. Transfection of RAR expression vectors in cultured cells activates heterologous promoters containing this sequence in vivo. This response element contains a consensus AP-1 site TGACTCA and in vitro is bound by the Jun-Fos complex. Unexpectedly, cotransfection of Jun and Fos expression vectors suppresses basal level transcription of the osteocalcin gene and suppresses induction by both retinoic acid and vitamin D3. Additional studies delimit an 11 nucleotide segment as a minimal hormone response element containing the AP-1 site as its core. These results indicate that two distinct classes of transcription factors can recognize common regulatory sequences, a phenomenon we refer to as cross-coupling.

摘要

我们提供的证据表明,人类骨钙素基因中的维生素D反应元件赋予了对维生素A代谢产物视黄酸的反应性。在大肠杆菌中表达的视黄酸受体(RAR)在体外与该序列结合。在培养细胞中转染RAR表达载体可在体内激活含有该序列的异源启动子。该反应元件包含一个共有AP-1位点TGACTCA,并且在体外被Jun-Fos复合物结合。出乎意料的是,Jun和Fos表达载体的共转染抑制了骨钙素基因的基础水平转录,并抑制了视黄酸和维生素D3的诱导作用。进一步的研究确定了一个11个核苷酸的片段作为最小的激素反应元件,其核心为AP-1位点。这些结果表明,两类不同的转录因子可以识别共同的调控序列,我们将这种现象称为交叉偶联。

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