Nishikawa J, Kitaura M, Matsumoto M, Imagawa M, Nishihara T
Department of Environmental Biochemistry, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Nucleic Acids Res. 1994 Aug 11;22(15):2902-7. doi: 10.1093/nar/22.15.2902.
Nuclear receptors for the thyroid hormone and vitamin A and D cooperate with the retinoid X receptor (RXR) in activating the transcription. Although the hormone response elements for these receptors have been proposed in which spacing of the direct repeated motifs determine the specificity (so called 3-4-5 rule), vitamin D response elements (VDREs) in the natural context consist of often imperfect direct repeats. Vitamin D receptor (VDR) alone can bind to the mouse osteopontin (mSPP-1) VDRE, which contains a direct repeat separated by 3 nucleotides, but not to the rat osteocalcin (rOST) VDRE having inexact direct repeat. The presence of RXR not only allows the VDR to bind to the rOST VDRE, but also increases the binding affinity for the mSPP-1 VDRE. The RXR/VDR heterodimer exhibits the similar affinity constants for the mSPP-1 VDRE and the rOST VDRE, in spite of the apparently different affinities for two VDREs of the VDR homodimer. A random oligonucleotide selection procedure revealed that the consensus sequence selected by the RXR homodimer is the direct repeat spaced by one A residue. In contrast, the sequences preferentially selected by the VDR homodimer and the VDR/RXR heterodimer are similar, which are the direct repeats spaced by 3 nucleotides. The difference and similarity of DNA sequence recognition are discussed.
甲状腺激素、维生素A和维生素D的核受体与视黄酸X受体（RXR）协同作用以激活转录。尽管已经提出了这些受体的激素反应元件，其中直接重复基序的间距决定了特异性（即所谓的3-4-5规则），但天然环境中的维生素D反应元件（VDRE）通常由不完美的直接重复序列组成。单独的维生素D受体（VDR）可以与小鼠骨桥蛋白（mSPP-1）的VDRE结合，该元件包含一个由3个核苷酸隔开的直接重复序列，但不能与具有不精确直接重复序列的大鼠骨钙素（rOST）的VDRE结合。RXR的存在不仅使VDR能够与rOST的VDRE结合，还增加了对mSPP-1的VDRE的结合亲和力。尽管VDR同二聚体对两种VDRE的亲和力明显不同，但RXR/VDR异二聚体对mSPP-1的VDRE和rOST的VDRE表现出相似的亲和常数。随机寡核苷酸筛选程序表明，RXR同二聚体选择的共有序列是由一个A残基隔开的直接重复序列。相反，VDR同二聚体和VDR/RXR异二聚体优先选择的序列相似，都是由3个核苷酸隔开的直接重复序列。本文讨论了DNA序列识别的差异和相似性。
