Näär A M, Boutin J M, Lipkin S M, Yu V C, Holloway J M, Glass C K, Rosenfeld M G
Eukaryotic Regulatory Biology Program, University of California, San Diego School of Medicine, La Jolla 92093-0648.
Cell. 1991 Jun 28;65(7):1267-79. doi: 10.1016/0092-8674(91)90021-p.
Characterization of several thyroid hormone (T3), retinoic acid, and estrogen response elements has led to the identification of conserved DNA half-sites (core binding motifs). We present evidence that differences in both the relative orientation and spacing of these motifs within hormone response elements determine the distinct transcriptional responses of three members of the nuclear receptor superfamily. When separated by 3 bp, direct repeat, palindromic, and inverted palindromic arrangements of these motifs impart selective transcriptional responses to retinoic acid, estrogen, and T3 receptors, respectively. Varying the spacing between core motifs alters the specificity. Without spacing, a direct repeat of the core motif paradoxically configures the T3 receptor to confer transactivation in the absence of T3 and repression in its presence. Such an element occurs naturally in the mouse beta-thyrotropin promoter, physiologically under negative regulation by T3. The orientation and spacing of core binding motifs may thus function in concert as a code that accounts for the selective patterns of transcriptional responses of hormonally regulated promoters.
对几种甲状腺激素（T3）、视黄酸和雌激素反应元件的特性分析已导致保守DNA半位点（核心结合基序）的鉴定。我们提供的证据表明，激素反应元件内这些基序的相对方向和间距差异决定了核受体超家族三个成员不同的转录反应。当这些基序被3个碱基对隔开时，直接重复、回文和反向回文排列分别赋予视黄酸、雌激素和T3受体选择性转录反应。改变核心基序之间的间距会改变特异性。没有间距时，核心基序的直接重复反而会使T3受体在没有T3时具有反式激活作用，而在有T3时具有抑制作用。这样一个元件自然存在于小鼠β-促甲状腺素启动子中，在生理上受T3的负调控。因此，核心结合基序的方向和间距可能协同发挥作用，作为一种密码，解释了激素调节启动子转录反应的选择性模式。
