Regulation of the human papillomavirus type 16 late promoter by transcriptional elongation.
Regulation of the human papillomavirus type 16 late promoter by transcriptional elongation.
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DOI：
10.1016/j.virol.2017.04.021
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发表时间：
2017-07
期刊：
影响因子：
3.7
通讯作者：
Bodily JM
中科院分区：
文献类型：
--
作者：
Songock WK;Scott ML;Bodily JM
来自人乳头瘤病毒16型（HPV 16）晚期启动子的转录物在宿主细胞分化时上调。分化依赖的转录调控被认为是隔离病毒抗原在最上层的上皮层，促进免疫逃避。在分化过程中调节晚期启动子上调的机制的特点很差。我们发现，晚期启动子在转录水平上调，病毒增强子刺激启动子活性。使用激酶抑制和染色质免疫沉淀分析，我们显示了转录延长的分化依赖性增强的证据。促进转录物延伸的三种因子，细胞周期蛋白依赖性激酶9（CDK9）、CDK8（介体复合物的亚基）和含溴结构域蛋白4（Brd4）在分化时被募集到病毒基因组中，并且各自在启动子活性中起作用。这些结果揭示了HPV16在病毒生命周期中用于正确调节基因表达的转录过程。
Transcripts from the late promoter of human papillomavirus type 16 (HPV16) are upregulated upon host cell differentiation. Differentiation-dependent transcript regulation is thought to sequester viral antigens in the uppermost epithelial layers, facilitating immune evasion. The mechanisms regulating late promoter upregulation during differentiation are poorly characterized. We show that the late promoter is upregulated at the transcriptional level and that the viral enhancer stimulates promoter activity. Using kinase inhibition and chromatin immunoprecipitation analysis, we show evidence for differentiation-dependent enhancement of transcript elongation. Three factors that promote transcript elongation, cyclin dependent kinase 9 (CDK9), CDK8 (a subunit of the Mediator complex), and bromodomain containing protein 4 (Brd4) are recruited to viral genomes upon differentiation, and each plays a role in promoter activity. These results shed light on the transcriptional processes utilized by HPV16 for proper regulation of gene expression during the viral life cycle.