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Nucleic Acids Research, 1993, Vol. 21, No. 4 1019-1023
© 1993

MOLECULAR BIOLOGY

The octamer binding site in the HPV16 regulatory region produces opposite effects on gene expression in cervical and non-cervical cells

Peter J. Morris, Carolyn L. Dent+, Christopher J. Ring and David S. Latchman*

Medical Molecular Biology Unit, Department of Biochemistry, Division of Molecular Pathology, University College London School of Medicine The Windeyer Building, Cleveland Street, London W1P 6DB, UK

* To whom correspondence should be addressed

Received September 24, 1992. Revised January 18, 1993. Accepted January 18, 1993.

The upstream regulatory region (URR) of the tumorigenic human papillomaviruses HPV 16 and 18 contains an octamer binding site which is located adjacent to a binding site for the ublquitous transcription factor NFI. The octamer site binds both the constitutively expressed transcription factor Oct-1 and a novel cervical octamer binding protein. In contrast the URR of the non-tumorigenic viruses HPV6 and HPV11 lacks the octamer binding site although the adjacent NFI site is conserved. Inactivation of the octamer binding site results in a higher level of gene expression in cells which contain only Oct-1 and a lower level in cells containing the cervical octamer binding protein indicating that whilst Oct-1 binding reduces promoter activity, the cervical protein increases it. In agreement with this, over-expression of Oct-1 reduces the level of gene activity directed by this region of the HPV 16/18 URR and inhibits its activation by NFI whilst having no effect on the corresponding region of the HPV 6/11 URR. The significance of these effects is discussed in terms of the cervical-specific activity of the HPV16/18 URR and its role in HPV-mediated transformation.

+ Present address: Wellcome Foundation Ltd., Langley Court, Beckenham, Kent BR3 3BS, UK


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