Human papillomavirus type 6 (HPV-6) DNA is the predominant HPV type found in condyloma acuminata: it is rarely found in carcinomas. We have previously reported cloning and characterizing an HPV-6 from a vulvar condyloma (HPV6-W50) and an HPV-6 from a vulvar carcinoma (HPV6-T70). The E5, E6 and E7 proteins encoded by the two genomes were identical, however, the two genomes differed in the long control region (LCR). Cloning of the entire LCR into the enhancerless plasmid pSVEcat showed that the two LCRs had comparable enhancer activity. Since the major differences between the two LCRs resided in the 5′ end of the LCR, upstream of the L1 polyadenylation signal, we subcloned the two LCRs to analyse more closely their effect on cat gene expression. The data indicated that LCR subclones of the two genomes had comparable chloramphenicol acetyltransferase (CAT) activity. A negative regulatory region was detectable when the test plasmids were transfected into HeLa and C33A cells and in primary keratinocytes. A decrease in CAT activity was also detected when the SV40 early promoter was replaced with the putative HPV-6 E6 promoter. The negative regulatory region functioned in a position- and orientation-independent manner, thus fulfilling the definition of a silencer.
AubornK. J.,
GalliR. L.,
DilorenzoT. P.,
SteinbergB. M.1989; Identification of DNA protein interactions and enhancer activity at the 5′ end of the upstream regulatory region in human papillomavirus type 11. Virology 170:123–130
AubornK. J.,
SteinbergB. M.1991; A key DNA-protein interaction determines the function of the 5′ URR enhancer in human papillomavirus type 11. Virology 181:132–138
BauknechtT.,
AngelP.,
RoyerH.-D.,
zur HausenH.1992; Identification of a negative regulatory domain in the human papillomavirus type 18 promoter: interaction with the transcriptional repressor YY1. EMBO Journal 11:4607–4617
BrandA. H.,
BreedenL.,
AbrahamJ.,
SternglanzR.,
NasmythK.1985; Characterization of a “silencer” in yeast: a DNA sequence with properties opposite to those of a transcriptional enhancer. Cell 41:41–48
ChongT.,
ChanW.-K.,
BernardH.-U.1990; Transcriptional activation of human papillomavirus 16 by nuclear factor 1, AP-1, steroid receptors and a possibly novel transcription factor, PVF: a model for the composition of genital papillomavirus enhancers. Nucleic Acids Research 18:465–470
ChongT.,
AptD.,
GlossB.,
IsaM.,
BernardH.-U.1991; The enhancer of human papillomavirus type 16: binding sites for the ubiquitous transcription factors oct-1, NFA, TEF-2, NF1, and AP-1 participate in epithelial cell-specific transcription. Journal of Virology 65:5933–5943
CripeT. P.,
HaugenT. H.,
TurkJ. P.,
TabatabaiF.,
SchmidP. G.,
DürstM.,
GissmannL.,
RomanA.,
TurekL. P.1987; Transcriptional regulation of the human papillomavirus-16 E6–E7 promoter by a keratinocyte-dependent enhancer and by viral E2 trans-activator and repressor gene products: implications for cervical carcinogenesis. EMBO Journal 6:3745–3753
CripeT. P.,
AlderbornA.,
AndersonR. D.,
ParkkinenS.,
BergmanP.,
HaugenT. H.,
PetterssonU.,
TurekL. P.1990; Transcriptional activation of the human papillomavirus-16 p97 promoter by an 88-nucleotide enhancer containing distinct cell-dependent and AP-1-responsive modules. New Biologist 2:450–463
CuthillS.,
SibbetG. J.,
CampoM. S.1993; Characterization of a nuclear factor, papilloma enhancer binding factor-1, that binds the long control region of human papillomavirus type 16 and contributes to enhancer activity. Molecular Carcinogenesis 8:96–104
DollardS. C.,
BrokerT. R.,
ChowL. T.1993; Regulation of the human papillomavirus type 11 E6 promoter by viral and host transcription factors in primary human keratinocytes. Journal of Virology 67:1721–1726
FarrA.,
WangH.,
KasherM. S.,
RomanA.1991; Relative enhancer activity and transforming potential of authentic human papillomavirus type 6 genomes from benign and malignant lesions. Journal of General Virology 72:519–526
GormanC. M.,
MoffatL. F.,
HowardB. H.1982; Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Molecular and Cellular Biology 2:1044–1051
HaugenT. H.,
CripeT. P.,
GinderG. D.,
KarinM.,
TurekL. P.1987; Tram-activation of an upstream early gene promoter of bovine papillomavirus-1 by a product of the viral E2 gene. EMBO Journal 6:145–152
IftnerT.,
OftM.,
BohmS.,
WilczynskiS. P.,
PfisterH.1992; Transcription of the E6 and E7 genes of human papillomavirus type 6 in anogenital condylomata is restricted to undifferentiated cell layers of the epidermis. Journal of Virology 66:4639–4646
JacksonM. E.,
CampoM. S.1991; Positive and negative E2-independent regulatory elements in the long control region of bovine papillomavirus type 4. Journal of General Virology 72:877–883
KasherM. S.,
RomanA.1988; Characterization of human papillomavirus type 6b DNA isolated from an invasive squamous carcinoma of the vulva. Virology 165:225–233
KyoS.,
InoueM.,
NishioY.,
NakanishiK.,
AkiraS.,
InoueH.,
YutsudoM.,
TanizawaO.,
HakuraA.1993; NF-IL6 represses early gene expression of human papillomavirus type 16 through binding to the noncoding region. Journal of Virology 67:1058–1066
KyoS.,
InoueM.,
HayasakaN.,
InoueT.,
YutsudoM.,
TanizawaO.,
HakuraA.1994; Regulation of early gene expression of human papillomavirus type 16 by inflammatory cytokines. Virology 200:130–139
Lopez-CabreraM.,
LetovskyJ.,
HuK.-Q.,
SiddiquiA.1990; Multiple liver-specific factors bind to the hepatitis B virus core/ pregenomic promoter: trans-activation and repression by CCAAT/ enhancer binding protein. Proceedings of the National Academy of Sciences, USA 87:5069–5073
LucibelloF. C.,
SlaterE. P.,
JoossK. U.,
BeatoM.,
MullerR.1990; Mutual transrepression of Fos and the glucocorticoid receptor: involvement of a functional domain in Fos which is absent in FosB. EMBO Journal 9:2827–2834
MackD. H.,
LaiminsL. A.1991; A keratinocyte-specific transcription factor, KRF-1, interacts with AP-1 to activate expression of human papillomavirus type 18 in squamous epithelial cells. Proceedings of the National Academy of Sciences, USA 88:91029106
MayM.,
DongX.-P.,
Beyer-FinklerE.,
StubenrauchR.,
FuchsP. G.,
PfisterH.1994; The E6/E7 promoter of extrachromosomal HPV-16 DNA in cervical cancers escapes from cellular repression by mutation of target sequences for YY1. EMBO Journal 13:1460–1466
RandoR. F.,
LancasterW. D.,
HanP.,
LopezC.1986; The noncoding region of HPV-6vc contains two distinct transcriptional enhancing elements. Virology 155:545–556
RehH.,
PfisterH.1990; Human papillomavirus type 8 contains cis-active positive and negative transcriptional control sequences. Journal of General Virology 71:2457–2462
SchwarzE.,
DurstM.,
DemankowskiD.,
LattermannO.,
ZechR.,
WolfspergerE.,
SuhaiS.,
zur HausenH.1983; DNA sequence and genome organization of genital human papillomavirus type 6b. EMBO Journal 2:2341–2348
SchwarzE.,
FreeseU. K.,
GissmannL.,
MayerW.,
RoggenbuckB.,
StremlauA.,
zur HausenH.1985; Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature 314:111–114
StolerM. H.,
WolinskyS. M.,
WhitbeckA.,
BrokerT. R.,
ChowL. T.1989; Differentiation-linked human papillomavirus types 6 and 11 transcription in genital condylomata revealed by in situ hybridization with message-specific RNA probes. Virology 172:331–340
ThierryF.,
YanivM.1987; The BPV-1-E2 transacting protein can be either an activator or a repressor of the HPV-18 regulatory region. EMBO Journal 6:3391–3397
ThierryF.,
SpyrouG.,
YanivM.,
HowleyP.1992; Two AP-1 sites binding JunB are essential for human papillomavirus type 18 transcription in keratinocytes. Journal of Virology 66:3740–3748
UshikaiM.,
LaceM. J.,
YamakawaY.,
KonoM.,
AnsonJ.,
IshijiT.,
ParkkinenS.,
WickerN.,
ValentineM.-E.,
DavidsonI.,
TurekL. P.,
HaugenT. H.1994; Trans activation by the full-length E2 proteins of human papillomavirus type 16 and bovine papillomavirus type 1 in vitro and in vivo: cooperation with activation domains of cellular transcription factors. Journal of Virology 68:6655–6666
WuY.-J.,
ParkerM.,
BinderN. E.,
BeckettM. A.,
SinardJ. H.,
GriffithsC. T.,
RheinwaldJ. G.1982; The mesothelial keratins: a new family of cytoskeleton proteins identified in cultured mesothelial cells and nonkeratinizing epithelia. Cell 31:693–703