title: Clusters of nuclear factor I binding sites identify enhancers of several papillomaviruses but alone are not sufficient for enhancer function.
abstract: The long control region (LCR) of human papillomaviruses (HPV) encompasses 5-12% of the viral genome and contains an intricate network of cis responsive elements. In the LCR of seven unrelated HPV-types, namely HPV-1, 6, 8, 11, 16, 18 and 33, we have identified clusters of 4 to 7 5-TTGGC-3 motifs suggesting nuclear factor I (NFI) binding sites. We randomly selected 20 (out of a total of 38) of these motifs and showed that pure NFI from porcine liver protects virtually the same nucleotides as a factor present in crude HeLa nuclear extracts. The footprints obtained with HeLa extracts in the LCR of HPV-16 are eliminated in competition experiments by an oligonucleotide representing the palindromic adenovirus NFI binding site. Restriction fragments from the genome of HPV-11, 16 and 18, which contain this cluster of NFI binding sites associated with binding sites of unrelated transcription factors, function as transcriptional enhancers. In contrast, a fragment from HPV-8 exhibiting exclusively NFI binding sites, or polymerized NFI sites from HPV-16, are functionally inactive. NFI seems to be necessary but not sufficient for HPV enhancer activation.
authors.affiliation: Institute of Molecular and Cell Biology, National University of Singapore, Kent Ridge, Republic of Singapore.
authors.forename: B
authors.initials: B
authors.lastname: Gloss
authors.forename: M
authors.initials: M
authors.lastname: Yeo-Gloss
authors.forename: M
authors.initials: M
authors.lastname: Meisterenst
authors.forename: L
authors.initials: L
authors.lastname: Rogge
authors.forename: E L
authors.initials: EL
authors.lastname: Winnacker
authors.forename: H U
authors.initials: HU
authors.lastname: Bernard
mesh_terms: D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002467:Cell Nucleus / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003850:Deoxyribonuclease I; D004742:Enhancer Elements, Genetic; D005814:Genes, Viral; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D027383:Papillomaviridae / Q000235:genetics*; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D003850:Deoxyribonuclease I