Py. Bourillot et al., TRANSCRIPTIONAL REPRESSION BY THE EPSTEIN-BARR-VIRUS EBNA3A PROTEIN TETHERED TO DNA DOES NOT REQUIRE RBP-J(KAPPA), Journal of General Virology, 79, 1998, pp. 363-370
The Epstein-Barr virus (EBV) proteins EBNA1, EBNA2, EBNA3A, EBNA3C, LM
P1 and EBNA-LP are essential for the in vitro immortalization of prima
ry B lymphocytes by EBV. EBNA2 is a transcriptional activator of viral
and cellular genes. Both EBNA3A and EBNA3C have been shown to specifi
cally inhibit EBNA2-activated transcription by direct interaction with
RBP-JK, a cellular DNA-binding factor known to recruit EBNA2 to EBNA2
-responsive genes. This interaction interferes with the binding of RBP
-JK to DNA in vitro, and this is probably the mechanism by which EBNA3
A and EBNA3C repress EBNA2-activated transcription in vivo. EBNA3A and
EBNA3C also directly repress transcription when tethered to a promote
r via the DNA-binding domain of the yeast Gal4 protein. As RBP-J kappa
has been previously shown to be a repressor in mam malian cells, this
repression could be due to the recruitment of RBP-J kappa by Gal4-EBN
A3A and 3C. In this study, we have precisely mapped the domain of EBNA
3A involved in the interaction with RBP-JK and we have shown that inte
raction with RBP-IK is not required for the Gal4-EBNA3A-mediated repre
ssion. Furthermore, we have characterized in EBNA3A a domain of 143 am
ino acids which is necessary and sufficient for EBNA3A-dependent repre
ssion.