YY1蛋白对HPV16启动子P97的抑制效应依赖于上游的增强子序列

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目的 观测位于HPV16LCR序列YY1结合位点上游的组织特异性增强子序列对YY1蛋白的启动子P97抑制作用的影响。方法 构建带有不同长度的HPV16野生株、启动子远端YY1位点突变株、启动子近端YY1位点突变株的 5′端LCR缺损序列的荧光素酶报导质粒 ,以及不同长度的近端YY1/SP1重叠结合位点基因工程突变LCR的荧光素酶报导质粒 ;将各种质粒转染到人类子宫颈癌细胞系C33A中 ,检测在不同LCR序列的控制下对病毒启动子P97的活性的影响。结果 去除上游增强子序列后 ,远端YY1位点突变的P97激活作用完全消失 ,近端YY1位点突变的P97激活作用部分丧失。不同长度的近端YY1/SP1重叠位点基因工程突变LCR对P97活性的影响不受上游启动子序列的控制。结论 YY1蛋白对启动子P97的抑制效应受位于其上游序列的增强子的控制 Objective To observe the effect of tissue-specific enhancer sequence located upstream of the YY1 binding site of HPV16 LCR sequence on the inhibition of P97 promoter of YY1 protein. Methods Luciferase reporter plasmids with different lengths of HPV16 wild-type strain, promoter distal YY1 locus mutant and promoter 5 ’LCR deletion mutant at the proximal YY1 locus of the promoter were constructed, YY1 / SP1 overlap binding site genetically engineered mutant LCR luciferase reporter plasmid; various plasmids were transfected into the human cervical cancer cell line C33A to detect the activity of the viral promoter P97 under the control of different LCR sequences influences. Results After removing the upstream enhancer sequence, the activation of P97 at the distal YY1 site disappeared completely, and the activation of P97 at the site of proximal YY1 mutation was partially lost. The effect of genetically engineered mutant LCRs with different lengths of proximal YY1 / SP1 overlapping sites on P97 activity was not controlled by the upstream promoter sequence. Conclusion The inhibitory effect of YY1 on promoter P97 is controlled by enhancers located in its upstream sequence
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