A switch region determines the cell type-specific positive or negative action of YY1 on the activity of the human papillomavirus type 18 promoter.
YY1 is a zinc finger transcription factor which acts as either a repressor or an activator dependent on the promoter context. YY1 is a potent activator of the genuine human papillomavirus type 18 (HPV-18) upstream regulatory region (URR) in HeLa cells, which are known for high-level expression of the HPV-18 early genes. The activating activity of YY1 is dependent on the presence of a newly identified switch region located upstream of the YY1 binding site. Deletion of this region causes YY1 to act as a repressor of HPV-18 promoter activity. In vivo footprinting of the HPV-18 URR and an in vitro electrophoretic mobility shift assay identified proteins binding to the switch region. Site-directed mutagenesis of the switch region and YY1 binding sites suggests that these two regions work in concert to yield high-level HPV-18 URR activity in HeLa cells but not in HepG2 cells, where HPV-18 is almost inactive. These data identified a novel mode of cell type-specific regulation of HPV-18 promoter activity by positive or negative action of YY1, determined by the switch region binding factor(s).
Bauknecht
T
T
Forschungsschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum Heidelberg, Germany.
Jundt
F
F
Herr
I
I
Oehler
T
T
Delius
H
H
Shi
Y
Y
Angel
P
P
Zur Hausen
H
H
D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D050986:YY1 Transcription Factor; D016335:Zinc Fingers
D017931:DNA Primers; D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D050981:Erythroid-Specific DNA-Binding Factors; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human