Bauknecht T, Angel P, Royer H D, zur Hausen H
Deutsches Krebsforschungszentrum Heidelberg, Germany.
EMBO J. 1992 Dec;11(12):4607-17. doi: 10.1002/j.1460-2075.1992.tb05563.x.
The human papillomavirus type 18 (HPV-18) promoter contains a TPA responsive element (TRE) which confers TPA responsiveness on a heterologous promoter. In the context of the HPV-18 promoter, however, this AP-1 site is inactive. We have identified a negative regulatory domain in the HPV-18 promoter which represses the constitutive and TPA-induced AP-1 activity. This negative regulatory sequence has been mapped to 44 nucleotides (OL13). We identified this element as a transcriptional silencer based on its ability to interfere with transcriptional initiation. This HPV-18 silencer domain was narrowed down further to 23 nucleotides, the OL13B element, which bears similarity to three other silencer sequences, present in the mouse N-ras gene upstream regulatory region, the mouse albumin gene enhancer and the adeno-associated virus P5 promoter. The transcriptional repressor protein YY1, which negatively regulates the P5 promoter, binds to the HPV-18 silencer with high affinity. Mutation of the YY1 binding site leads to an enhanced activity of the HPV-18 promoter, strongly suggesting that YY1 plays an important role in controlling HPV-18 early gene expression.
人乳头瘤病毒18型（HPV - 18）启动子含有一个佛波酯反应元件（TRE），该元件可赋予异源启动子对佛波酯的反应性。然而，在HPV - 18启动子的背景下，这个AP - 1位点是无活性的。我们已经在HPV - 18启动子中鉴定出一个负调控域，它可抑制组成型和佛波酯诱导的AP - 1活性。这个负调控序列已被定位到44个核苷酸（OL13）。基于其干扰转录起始的能力，我们将这个元件鉴定为转录沉默子。这个HPV - 18沉默子结构域进一步缩小到23个核苷酸，即OL13B元件，它与存在于小鼠N - ras基因上游调控区、小鼠白蛋白基因增强子和腺相关病毒P5启动子中的其他三个沉默子序列相似。对P5启动子起负调控作用的转录抑制蛋白YY1以高亲和力结合到HPV - 18沉默子上。YY1结合位点的突变导致HPV - 18启动子活性增强，这强烈表明YY1在控制HPV - 18早期基因表达中起重要作用。
