González-Manchón C, Ayuso M S, Parrilla R
Department of Pathophysiology and Human Molecular Genetics, Centro de Investigaciones Biológicas (CSIC), Velázquez 144, 28006, Madrid, Spain.
Gene. 1999 Jan 8;226(1):111-9. doi: 10.1016/s0378-1119(98)00543-5.
The human malic enzyme (hME) promoter contains an inverted palindromic (IP4) 3,5,3'-triiodo-thyronine (T3) response element (T3RE) 15bp downstream from an activating protein-1 (AP-1) site. The purpose of this study was to analyze the functional relationship between both cis-acting elements. The following observations indicate that these two elements operate as a functional unit in controlling the human ME gene:T3 failed to stimulate transcription above the basal levels in cells overexpressing either TRb or TRb/retinoid acid receptor (RXR), indicating that TRbeta acts primarily as a transcriptional repressor in the context of the hME. Moreover, the finding of a repressive effect of TRbeta without DNA binding suggests the existence of both DNA-dependent and independent mechanisms of TRbeta-induced repression of transcription.
人苹果酸酶(hME)启动子在激活蛋白-1(AP-1)位点下游15bp处含有一个反向回文(IP4)3,5,3'-三碘甲状腺原氨酸(T3)反应元件(T3RE)。本研究的目的是分析这两个顺式作用元件之间的功能关系。以下观察结果表明,这两个元件在控制人ME基因时作为一个功能单元发挥作用:在过表达TRβ或TRβ/视黄酸受体(RXR)的细胞中,T3未能刺激转录水平超过基础水平,这表明在hME的背景下,TRβ主要作为转录抑制因子发挥作用。此外,TRβ无DNA结合时具有抑制作用这一发现表明,存在TRβ诱导转录抑制的DNA依赖性和非依赖性机制。