Overlapping YY1- and aberrant SP1-binding sites proximal to the early promoter of human papillomavirus type 16.
Transcription of oncogenes E6 and E7 of human papillomavirus type 16 (HPV-16) from the P97 promoter is regulated by viral and cellular proteins. The transcription factor YY1 represses transcription through binding to cognate sequences in the long control region (LCR). In HPV-16 DNA from cervical carcinomas, mutations of YY1-binding sites have been identified that increase P97 activity 3-6-fold. A second, SP1-binding site has now been identified in the HPV-16 LCR (nt 7842-7847), which overlaps the YY1-binding site at positions 7840-7848. A point mutation within this YY1 site in viral DNA from a cervical cancer, previously shown to prevent YY1 binding, was shown to increase SP1 binding and P97 activity 4.7-fold. An engineered mutant eliminating SP1 binding showed only 1- to 1.6-fold increased P97 activity. It is concluded that competition between SP1 and YY1 for DNA binding plays a major role in YY1 repression mediated by the binding site at positions 7840-7848.
Dong
Xiao-Ping
XP
Institute of Virology, Universität zu Köln, Fürst-Pückler Str. 56, 50935 Köln, Germany1.
Pfister
Herbert
H
Institute of Virology, Universität zu Köln, Fürst-Pückler Str. 56, 50935 Köln, Germany1.
D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D015967:Gene Expression Regulation, Viral; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D050986:YY1 Transcription Factor
D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; D050981:Erythroid-Specific DNA-Binding Factors; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C059731:oncogene protein E7, Human papillomavirus type 16