title: 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 development. Although transcription activation by Rta is frequently associated with the binding of Rta to the Rta-response element (RRE) in promoters, Rta sometimes activates promoters without an RRE. Here we show that Rta interacts with an Sp1-interacting protein, MBD1-containing chromatin-associated factor 1 (MCAF1). This interaction is critical to the formation of an Sp1-MCAF1-Rta complex at Sp1 sites. Therefore, following lytic induction and the expression of Rta, Rta increases Sp1-mediated transcription. The genes that are thus activated include p16, p21, 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 the expression of Rta and Zta from EBV, indicating that MCAF1 participates EBV lytic activation. Our study documents the critical role of Rta in regulating the transcription of the genes that are mediated by Sp1.
authors.affiliation: Faculty of Biological Medicine and Environmental Biology and Graduate Institute of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Li-Kwan
authors.initials: LK
authors.lastname: Chang
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Chung
authors.forename: Yi-Ren
authors.initials: YR
authors.lastname: Hong
authors.forename: Takaya
authors.initials: T
authors.lastname: Ichimura
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Nakao
authors.forename: Shih-Tung
authors.initials: ST
authors.lastname: Liu
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D047468:Immunoprecipitation; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins; D020218:Response Elements; D016329:Sp1 Transcription Factor / Q000032:analysis / Q000378:metabolism*; D015534:Trans-Activators / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins
chemical_list: C501309:ATF7IP protein, human; C068382:BRLF1 protein, Human herpesvirus 4; D017874:Immediate-Early Proteins; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins