Holloway J M, Glass C K, Adler S, Nelson C A, Rosenfeld M G
Eukaryotic Regulatory Biology Program, Center for Molecular Genetics, University of California, San Diego, School of Medicine, La Jolla 92093-0613.
Proc Natl Acad Sci U S A. 1990 Oct;87(20):8160-4. doi: 10.1073/pnas.87.20.8160.
To investigate mechanisms responsible for positive and negative transcriptional control, we have utilized two types of promoters that are differentially regulated by thyroid hormone (T3) receptors. Promoters containing the palindromic T3 response element TCAGGTCA TGACCTGA are positively regulated by the T3 receptor after the administration of T3, whereas otherwise identical promoters containing the estrogen response element TCAGGTCA CTG TGACCTGA can be regulated negatively; converse effects are observed with the estrogen receptor. We describe evidence that the transcriptional inhibitory effects of the T3 or estrogen receptors on the estrogen or T3 response elements, respectively, are imposed by amino acid sequences in the C'-terminal region that colocalize with dimerization and hormone-binding domains and that these sequences can transfer inhibitory functions to other classes of transcription factors. Removal of the C'-terminal dimerization and hormone-binding domains of either the alpha T3 or estrogen receptors permits each receptor to act constitutively to enhance transcription on both T3 and estrogen response elements. It is, therefore, suggested that protein-protein interactions between receptor C' termini limit the subset of DNA binding sites on which transcriptional activation occurs.
为了研究负责正负转录调控的机制，我们利用了两种受甲状腺激素（T3）受体差异调控的启动子。含有回文T3反应元件TCAGGTCA TGACCTGA的启动子在给予T3后受T3受体正向调控，而含有雌激素反应元件TCAGGTCA CTG TGACCTGA的其他相同启动子则可被负向调控；雌激素受体则观察到相反的效应。我们描述的证据表明，T3或雌激素受体分别对雌激素或T3反应元件的转录抑制作用是由C末端区域的氨基酸序列施加的，这些序列与二聚化和激素结合域共定位，并且这些序列可以将抑制功能转移到其他类别的转录因子。去除αT3或雌激素受体的C末端二聚化和激素结合域可使每个受体组成性地发挥作用，以增强T3和雌激素反应元件上的转录。因此，提示受体C末端之间的蛋白质-蛋白质相互作用限制了发生转录激活的DNA结合位点的子集。
