Target genes of RORα which controls postnatal development of cerebeller Purkinje cells

我们分析了三个基因的转录调控机制，这三个基因分别是pcp-2、丙皂苷和5-脂氧合酶基因，它们在浦肯野细胞中表达并含有一个RoRα反应元件(RORE)。不含糖皮质激素反应元件的pCP-2基因依赖于RoRα的转录被糖皮质激素受体(GR)抑制。反之，RoRα可抑制MMTV启动子的GR依赖转录。转录拮抗所必需的区域分别定位于GR的N端和RoRα的C端。由于RoRα和GR之间不存在直接相互作用，因此推测RoRα和GR所共有的一种新的介体可能在转录水平上具有拮抗作用。丙皂苷基因(PSAP)含有一个与RoRα有效结合的RORE。虽然RoRα激活了与PSAP基因RORE连锁的tk基因启动子的转录，但在P19和HeLa细胞中均不能激活PSAP基因的转录。相反，与PSAP基因连锁的GRE在P19中未能激活PSAP基因的转录，但在HeLa细胞中激活了转录。这些结果表明，核受体的转录激活既依赖于启动子类型，也依赖于细胞类型。由于真核细胞裂解基因的启动子具有结构多样性，在启动子上形成的基础转录复合体可能不同。核受体与其同源反应元件与基础转录复合体的相互作用不同。5-脂氧合酶(5-LO)基因的转录已被RoRα抑制。我们最近观察到，转录抑制是由于ACTC作为该基因的反式激活因子而抑制了Egr1的功能。

We analyzed regulatory mechanisms of transcription of three genes, Pcp-2, prosaposin and 5-lipoxygenase genes, which are expressed in the Purkinje cells and contain a RORα-responsive elemenet (RORE). RORα-dependent transcription of the Pcp-2 gene which does not contain a glucocorticoid responsive element was shown to be repressed by glucocorticoid receptor (GR). Reciprocally, GR-dependent transcription of MMTV promoter was repressed by RORα. Regions essential for the transcriptional antagonism was mapped to the N-terminus of GR and the C-terminus of RORα, respectively. Since RORα and GR did not directly interact each other, it was suggested that a novel mediator common for RORα and GR confers the transcriptional antagonism between them.Prosaposin gene (pSAP) contains a RORE which is efficiently bound with RORα. Although RORα activated transcription of the tk gene promoter linked with the RORE of pSAP gene, it failed to activate transcription of pSAP gene both in P19 and HeLa cells. In contrast, although GRE linked to pSAP gene failed to activate its transcription in P19, it activated the transcription in HeLa cells. These results indicated that transcriptional activation by nuclear receptors is dependent both on type of promoter and cell-type. Since promoters of eukaryptic genes show a structural variety, basal transcriptional complex formed on the promoter might differ from one to another. Nuclear receptor bound with its cognate responsive element interact differently to the basal transcription complex.Transcription of 5-lipoxygenase (5-LO) gene has been demonstrated to be repressed by RORα. We recently observed that the transcriptional repression results from suppression of EGR1 function which actc as a transactivator of this gene.