Activation of Sp1-mediated transcription by Rta of Epstein-Barr virus via an interaction with MCAF1.

Abstract

Rta is a transcription factor encoded by BRLF1 of the Epstein-Barr virus (EBV). This factor is expressed during the immediate-early stage of the lytic cycle to activate the genes required for EBV lytic develop- ment. Although transcription activation by Rta is 15 frequently associated with the binding of Rta to the Rta-response element (RRE) in promoters, Rta some- times activates promoters without an RRE. Here we show that Rta interacts with an Sp1-interacting pro- tein, MBD1-containing chromatin-associated factor 1 20 (MCAF1). This interaction is critical to the forma- tion of an Sp1-MCAF1-Rta complex at Sp1 sites. Therefore, following lytic induction and the expres- sion of Rta, Rta increases Sp1-mediated transcription. The genes that are thus activated include p16, p21, 25 SNRPN and BRLF1. However, the binding of Rta to RRE prevents the interaction between Rta and MCAF1; therefore, transcription activation by RRE depends only on Rta, and not on MCAF1 or Sp1. Furthermore, this study finds that MCAF1 promotes 30 the expression of Rta and Zta from EBV, indicating that MCAF1 participates EBV lytic activation. Our study documents the critical role of Rta in regulat- ing the transcription of the genes that are mediated by Sp1.