Vaccaro M, Pawlak A, Jost J P
Friedrich Miescher-Institute, Basel, Switzerland.
Proc Natl Acad Sci U S A. 1990 Apr;87(8):3047-51. doi: 10.1073/pnas.87.8.3047.
A homologous in vitro transcription system was developed in which the cloned chicken vitellogenin II gene is faithfully transcribed by extracts prepared from chicken liver nuclei. The use of template deleted of its upstream region resulted in poor transcriptional efficiency, as did the use of extracts prepared from rooster liver, in which the gene is silent. The influence of individual cis elements was determined by transcription competition analysis. Oligonucleotides covering greater than 500 base pairs of the promoter region were used as competitor DNA in the in vitro reactions. Competition with an oligonucleotide covering part of the expression-specific DNase I hypersensitivity site B2, which contains a demethylation site, mCpG, at nucleotide position + 10, increased transcription of the gene, suggesting the binding of a repressor to this region. The enhancement of transcription was even more pronounced when the same oligonucleotide was methylated at the corresponding + 10 cytosine. Competition with oligonucleotides covering the TATA box, or the estrogen response element half-palindromic motif (GGTCA) at nucleotide positions -198 to -194, resulted in a large decrease in vitellogenin gene transcription, indicating that strongly activating factors bind to these regions. Competing oligonucleotides covering other GGTCA-containing motifs situated further upstream at nucleotide positions -292 to -288, -367 to -351, and -626 to -614 were increasingly less effective in inhibiting transcription. The results indicate that factors other than the estrogen receptor are involved in transcriptional activation of the vitellogenin II gene.
我们开发了一种同源体外转录系统,其中克隆的鸡卵黄蛋白原II基因可被从鸡肝细胞核制备的提取物准确转录。使用缺失其上游区域的模板会导致转录效率低下,使用从公鸡肝脏制备的提取物(其中该基因处于沉默状态)时也是如此。通过转录竞争分析确定了各个顺式元件的影响。覆盖启动子区域超过500个碱基对的寡核苷酸被用作体外反应中的竞争DNA。与覆盖表达特异性DNase I超敏位点B2一部分的寡核苷酸竞争,该位点在核苷酸位置+10处含有一个去甲基化位点mCpG,可增加该基因的转录,这表明有一个阻遏物结合到该区域。当相同的寡核苷酸在相应的+10胞嘧啶处被甲基化时,转录增强更为明显。与覆盖TATA框或核苷酸位置-198至-194处的雌激素反应元件半回文基序(GGTCA)的寡核苷酸竞争,导致卵黄蛋白原基因转录大幅下降,表明有强激活因子结合到这些区域。覆盖位于更上游核苷酸位置-292至-288、-367至-351和-626至-614处其他含GGTCA基序的竞争寡核苷酸在抑制转录方面的效果越来越差。结果表明,除雌激素受体外的其他因子参与了卵黄蛋白原II基因的转录激活。