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J Biol Chem, Vol. 274, Issue 39, 27839-27844, September 24, 1999
An Enhanced Epithelial Response of a Papillomavirus Promoter to
Transcriptional Activators
Keith W.
Vance,
M. Saveria
Campo, and
Iain M.
Morgan
From the Beatson Institute for Cancer Research, Cancer Research
Campaign Beatson Laboratories, Garscube Estate,
Glasgow G61 1BD, Scotland
Mucosal epitheliotropic papillomaviruses have a
similar long control region (LCR) organization: a promoter region, an
enhancer region, and a highly conserved distribution of E2 DNA binding sites. The enhancer of these viruses is epithelial-specific, as it
fails to activate transcription from heterologous promoters in
nonepithelial cell types (Gloss, B., Bernard, H. U., Seedorf, K.,
and Klock, G. (1987) EMBO J. 6, 3735-3743; Morgan, I. M., Grindlay, G. J., and Campo, M. S. (1999) J. Gen. Virol. 80, 23-27). Studies on E2 transcriptional regulation
of the human mucosal epitheliotropic papillomaviruses have been
hindered by poor access to the natural target cell type and by the
observation that some of the human papillomavirus promoters, including
human papillomavirus-16, are repressed in immortalized epithelial
cells. Here we present results using the bovine papillomavirus-4
(BPV-4) LCR and a bovine primary cell system as a model to study the
mechanism of E2 transcriptional regulation of mucosal epitheliotropic
papillomaviruses and the cell type specificity of this regulation. E2
up-regulates transcription from the BPV-4 LCR preferentially in
epithelial cells (Morgan, I. M., Grindlay, G. J., and Campo, M. S. (1998) J. Gen. Virol. 79, 501-508). We demonstrate that
the epithelial-specific enhancer element of the BPV-4 LCR is not
required for the enhanced activity of E2 in epithelial cells and that
the BPV-4 promoter is more responsive, not only to E2, but to other
transcriptional activators in epithelial cells. This is the first time
a level of epithelial specificity has been shown to reside in a
papillomavirus promoter region.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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