REPRESSION BY RAZ OF EPSTEIN-BARR-VIRUS BZIP TRANSCRIPTION FACTOR EB1IS DIMERIZATION INDEPENDENT

The hallmark of Epstein-Barr virus (EBV) infection is the establishmen t of a viral genome transcription pattern called latency, The EBV BZLF 1 gene product EB1 (also known as ZEBRA or Zta) is a transcription fac tor which is essential for the switch from latency to the lytic cycle. It has been proposed that latency is maintained (i) by the inhibition of EB1 translation via antisense hybridization of EBNA1 and EB1 hnRNA s, or (ii) by the inactivation of the EB1 activating function via the direct interaction of EB1 with RelA, the retinoic acid receptor and p5 3, or via the titration of EB1 in RAZ:EB1 inactive heterodimers that a re unable to bind to DNA, RAZ, a fusion protein which contains the EB1 C-terminal dimerization and DNA-binding domains fused to the N-termin al 86 amino acids of the EBV BRLF1 gene product R, has been described as a trans-dominant negative regulator of EB1-activated transcription, We demonstrate here that although RAZ efficiently represses EB1-media ted transcriptional activation, the amount of RAZ protein expressed is incompatible with repression through the titration of EB1 in inactive EB1 :RAZ heterodimers. Furthermore, we also demonstrate that RAZ effi ciently represses transcription activated by an EB1 mutant carrying th e GCN4 homodimerization domain (EB1(gcn4)), despite the inability of R AZ and EB1(gcn4) to form stable heterodimers.