The family of repeats (FR) is a major upstream enhancer of the Epstein–Barr virus (EBV) latent C promoter (Cp) that controls transcription of six different latent nuclear proteins following interaction with the EBV nuclear protein EBNA1. Here, it was shown that Cp could also be activated by octamer-binding factor (Oct) proteins. Physical binding to the FR by the cellular transcription factors Oct-1 and Oct-2 was demonstrated by using an electrophoretic mobility-shift assay. Furthermore, Oct-1 in combination with co-regulator Bob.1, or Oct-2 alone, could drive transcription of a heterologous thymidine kinase promoter linked to the FR in both B cells and epithelial cells. Cp controlled by the FR was also activated by binding of Oct-2 to the FR. This may have direct implications for B cell-specific regulation of Cp.
AmbinderR. F.,
ShahW. A.,
RawlinsD. R.,
HaywardG. S.,
HaywardS. D.1990; Definition of the sequence requirements for binding of the EBNA-1 protein to its palindromic target sites in Epstein-Barr virus DNA. J Virol 64:2369–2379
Ben-BassatH.,
GoldblumN.,
MitraniS.7 other authors1977; Establishment in continuous culture of a new type of lymphocyte from a “Burkitt like” malignant lymphoma (line D.G.-75. Int J Cancer 19:27–33[CrossRef]
BoreströmC.,
ZetterbergH.,
LiffK.,
RymoL.2003; Functional interaction of nuclear factor Y and Sp1 is required for activation of the Epstein-Barr virus C promoter. J Virol 77:821–829[CrossRef]
ChenF.,
ZouJ.-Z.,
di RenzoL.,
WinbergG.,
HuL.-F.,
KleinE.,
KleinG.,
ErnbergI.1995; A subpopulation of normal B cells latently infected with Epstein-Barr virus resembles Burkitt lymphoma cells in expressing EBNA-1 but not EBNA-2 or LMP1. J Virol 69:3752–3758
DasG.,
HerrW.1993; Enhanced activation of the human histone H2B promoter by an Oct-1 variant generated by alternative splicing. J Biol Chem 268:25026–25032
DawsonS. J.,
YoonS. O.,
ChikaraishiD. M.,
LillycropK. A.,
LatchmanD. S.1994; The Oct-2 transcription factor represses tyrosine hydroxylase expression via a heptamer TAATGARAT-like motif in the gene promoter. Nucleic Acids Res 22:1023–1028[CrossRef]
ErnbergI.,
FalkK.,
MinarovitsJ.,
BussonP.,
TurszT.,
MasucciM. G.,
KleinG.1989; The role of methylation in the phenotype-dependent modulation of Epstein–Barr nuclear antigen 2 and latent membrane protein genes in cells latently infected with Epstein–Barr virus. J Gen Virol 70:2989–3002[CrossRef]
GahnT. A.,
SugdenB.1995; An EBNA-1-dependent enhancer acts from a distance of 10 kilobase pairs to increase expression of the Epstein-Barr virus LMP gene. J Virol 69:2633–2636
JinX. W.,
SpeckS. H.1992; Identification of critical cis elements involved in mediating Epstein-Barr virus nuclear antigen 2-dependent activity of an enhancer located upstream of the viral Bam HI C promoter. J Virol 66:2846–2852
JonesC. H.,
HaywardS. D.,
RawlinsD. R.1989; Interaction of the lymphocyte-derived Epstein-Barr virus nuclear antigen EBNA-1 with its DNA-binding sites. J Virol 63:101–110
KleinG.,
DombosL.,
GothoskarB.1972; Sensitivity of Epstein–Barr virus (EBV) producer and non-producer human lymphoblastoid cell lines to superinfection with EB-virus. Int J Cancer 10:44–57[CrossRef]
Längle-RouaultF.,
PatzelV.,
BenaventeA.,
TaillezM.,
SilvestreN.,
BompardA.,
SczakielG.,
JacobsE.,
RittnerK.1998; Up to 100-fold increase of apparent gene expression in the presence of Epstein-Barr virus oriP sequences and EBNA1: implications of the nuclear import of plasmids. J Virol 72:6181–6185
LevitskayaJ.,
CoramM.,
LevitskyV.,
ImrehS.,
Steigerwald-MullenP. M.,
KleinG.,
KurillaM. G.,
MasucciM. G.1995; Inhibition of antigen processing by the internal repeat region of the Epstein–Barr virus nuclear antigen-1. Nature 375:685–688[CrossRef]
LillycropK. A.,
LatchmanD. S.1992; Alternative splicing of the Oct-2 transcription factor RNA is differentially regulated in neuronal cells and B cells and results in protein isoforms with opposite effects on the activity of octamer/TAATGARAT-containing promoters. J Biol Chem 267:24960–24965
LiuY.-Z.,
LillycropK. A.,
LatchmanD. S.1995; Regulated splicing of the Oct-2 transcription factor RNA in neuronal cells. Neurosci Lett 183:8–12[CrossRef]
MüllerM. M.,
RuppertS.,
SchaffnerW.,
MatthiasP.1988; A cloned octamer transcription factor stimulates transcription from lymphoid-specific promoters in non-B cells. Nature 336:544–551[CrossRef]
NilssonT.,
SjöblomA.,
MasucciM. G.,
RymoL.1993; Viral and cellular factors influence the activity of the Epstein-Barr virus BCR2 and BWR1 promoters in cells of different phenotype. Virology 193:774–785[CrossRef]
NilssonT.,
ZetterbergH.,
WangY. C.,
RymoL.2001; Promoter-proximal regulatory elements involved in oriP -EBNA1-independent and -dependent activation of the Epstein-Barr virus C promoter in B-lymphoid cell lines. J Virol 75:5796–5811[CrossRef]
RawlinsD. R.,
MilmanG.,
HaywardS. D.,
HaywardG. S.1985; Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region. Cell 42:859–868[CrossRef]
ReismanD.,
SugdenB.1986; trans activation of an Epstein-Barr viral transcriptional enhancer by the Epstein-Barr viral nuclear antigen 1. Mol Cell Biol 6:3838–3846
ScheidereitC.,
HeguyA.,
RoederR. G.1987; Identification and purification of a human lymphoid-specific octamer-binding protein (OTF-2) that activates transcription of an immunoglobulin promoter in vitro. Cell 51:783–793[CrossRef]
SturmR. A.,
DasG.,
HerrW.1988; The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. Genes Dev 2:1582–1599[CrossRef]
SugdenB.,
WarrenN.1989; A promoter of Epstein-Barr virus that can function during latent infection can be transactivated by EBNA-1, a viral protein required for viral DNA replication during latent infection. J Virol 63:2644–2649
SungN. S.,
KenneyS.,
GutschD.,
PaganoJ. S.1991; EBNA-2 transactivates a lymphoid-specific enhancer in the Bam HI C promoter of Epstein-Barr virus. J Virol 65:2164–2169
SungN. S.,
WilsonJ.,
DavenportM.,
SistaN. D.,
PaganoJ. S.1994; Reciprocal regulation of the Epstein-Barr virus Bam HI-F promoter by EBNA-1 and an E2F transcription factor. Mol Cell Biol 14:7144–7152
TanakaM.,
GrossniklausU.,
HerrW.,
HernandezN.1988; Activation of the U2 snRNA promoter by the octamer motif defines a new class of RNA polymerase II enhancer elements. Genes Dev 2:1764–1778[CrossRef]
TomilinA.,
ReményiA.,
LinsK.,
BakH.,
LeidelS.,
VriendG.,
WilmannsM.,
SchölerH. R.2000; Synergism with the coactivator OBF-1 (OCA-B, BOB-1) is mediated by a specific POU dimer configuration. Cell 103:853–864[CrossRef]
WirthT.,
PriessA.,
AnnweilerA.,
ZwillingS.,
OelerB.1991; Multiple Oct2 isoforms are generated by alternative splicing. Nucleic Acids Res 19:43–51[CrossRef]
WysokenskiD. A.,
YatesJ. L.1989; Multiple EBNA1-binding sites are required to form an EBNA1-dependent enhancer and to activate a minimal replicative origin within oriP of Epstein-Barr virus. J Virol 63:2657–2666
YatesJ.,
WarrenN.,
ReismanD.,
SugdenB.1984; A cis -acting element from the Epstein–Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells. Proc Natl Acad Sci U S A 81:3806–3810[CrossRef]
ZetterbergH.,
BoreströmC.,
NilssonT.,
RymoL.2004; Multiple EBNA1-binding sites within oriPI are required for EBNA1-dependent transactivation of the Epstein-Barr virus C promoter. Int J Oncol 25:693–696