The octamer binding site in the HPV16 regulatory region produces opposite effects on gene expression in cervical and non-cervical cells.
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 ubiquitous 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 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.
Department of Biochemistry, University College London School of Medicine, UK.
P J
PJ
Morris
C L
CL
Dent
C J
CJ
Ring
D S
DS
Latchman
D001483:Base Sequence; D001665:Binding Sites / Q000502:physiology; D002584:Cervix Uteri / Q000378:metabolism / Q000382:microbiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006367:HeLa Cells; D051863:Host Cell Factor C1; D006801:Humans; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1; D009928:Organ Specificity; D027383:Papillomaviridae / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D014157:Transcription Factors