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Journal of Virology, December 1998, p. 10083-10092, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

A Novel YY1-Independent Silencer Represses the Activity of the Human Papillomavirus Type 16 Enhancer

Mark J. O'Connor, Walter Stünkel, Holger Zimmermann, Choon-Heng Koh, and Hans-Ulrich Bernard*

Institute of Molecular and Cell Biology, Singapore 117 609, Singapore

Received 14 July 1998/Accepted 14 September 1998

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.

* Corresponding author. Mailing address: Institute of Molecular and Cell Biology, 30 Medical Dr., Singapore 117 609, Singapore. Phone: (65) 8743765. Fax: (65) 7791117. E-mail: mcbhub{at}imcb.nus.edu.sg.

Journal of Virology, December 1998, p. 10083-10092, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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