title: A novel YY1-independent silencer represses the activity of the human papillomavirus type 16 enhancer.
abstract: Regulation of the human papillomavirus type 16 (HPV-16) E6 promoter is a complex process in which transcriptional repression as well as activation plays an important role. Here, we identify a negative regulatory element that in the context of a continuous long control region fragment overcomes the activation of the HPV-16 enhancer. This silencing element, which we have termed a PSM (papillomavirus silencing motif), consists of two copies of the sequence 5'-TAYAATAAT-3' that overlap the origin of replication. Each copy of this 9-bp sequence binds the same unknown cellular factor, which we refer to as PSM-BP (PSM binding protein). Both copies of the binding sequence are required for transcriptional repression, and we provide evidence that suggests that this particular organization results in the stabilization of a PSM-BP dimer. The silencing motif, while functioning in either orientation, showed a positional requirement between the enhancer and the promoter. Experiments with both a heterologous enhancer and a promoter also demonstrated a general ability of this element to function as a transcriptional silencer in non-HPV systems. Our findings provide an important addition to our understanding of HPV-16 gene regulation and an interesting model for the study of transcriptional repression.
authors.affiliation: Institute of Molecular and Cell Biology, Singapore 117 609, Singapore.
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Connor
authors.forename: W
authors.initials: W
authors.lastname: Stünkel
authors.forename: H
authors.initials: H
authors.lastname: Zimmermann
authors.forename: C H
authors.initials: CH
authors.lastname: Koh
authors.forename: H U
authors.initials: HU
authors.lastname: Bernard
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D050981:Erythroid-Specific DNA-Binding Factors; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic; D018741:Replication Origin; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D050986:YY1 Transcription Factor
chemical_list: D004279:DNA, Viral; 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; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C059731:oncogene protein E7, Human papillomavirus type 16