IDENTIFICATION OF A NEGATIVE REGULATORY DOMAIN IN THE HUMAN PAPILLOMAVIRUS TYPE-18 PROMOTER - INTERACTION WITH THE TRANSCRIPTIONAL REPRESSOR-YY1
IDENTIFICATION OF A NEGATIVE REGULATORY DOMAIN IN THE HUMAN PAPILLOMAVIRUS TYPE-18 PROMOTER - INTERACTION WITH THE TRANSCRIPTIONAL REPRESSOR-YY1
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DOI：
10.1002/j.1460-2075.1992.tb05563.x
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发表时间：
1992-12-01
期刊：
影响因子：
11.4
通讯作者：
HAUSEN, HZ
中科院分区：
文献类型：
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作者：
BAUKNECHT, T;ANGEL, P;HAUSEN, HZ
人乳头瘤病毒18型（HPV-18）启动子包含TPA应答元件（TRE），该元件在异源启动子上赋予TPA应答性。然而，在HPV-18启动子的情况下，这个AP-1位点是无活性的。我们已经在HPV-18启动子中发现了一个负调控域，它抑制了组成型和tpa诱导的AP-1活性。该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，我们将该元件确定为转录沉默者。该HPV-18沉默域进一步缩小到23个核苷酸，OL13B元件与小鼠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启动子中存在的其他三个沉默序列相似。转录抑制蛋白YY1负调控P5启动子，与HPV-18沉默子高亲和力结合。YY1结合位点的突变导致HPV-18启动子活性增强，强烈提示YY1在控制HPV-18早期基因表达中起重要作用。
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.