title: MCAF1 and Rta-activated BZLF1 transcription in Epstein-Barr virus.
abstract: Epstein-Barr virus (EBV) expresses two transcription factors, Rta and Zta, which are involved in the transcriptional activation of EBV lytic genes. This study sought to elucidate the mechanism by which Rta activates transcription of the Zta-encoding gene, BZLF1, through the ZII element in the gene promoter. In a DNA affinity precipitation assay, ATF2 was found to associate with an Rta-interacting protein, MCAF1, at the ZII element. The interaction between Rta, MCAF1, and ATF2 at the same site in the ZII region was further verified in vivo by chromatin immunoprecipitation assay. The complex appears to be crucial for the activation of BZLF1 transcription, as the overexpression of two ATF2-dominant negative mutants, or the introduction of MCAF1 siRNA into 293T cells, were both found to substantially reduce Rta-mediated transcription levels of BZLF1. Moreover, this study also found that the Rta-MCAF1-ATF2 complex binds to a typical AP-1 binding sequence on the promoter of BMRF2, a key viral gene for EBV infection. Mutation of this sequence decreased Rta-mediated promoter activity significantly. Taken together, these results indicate a critical role for MCAF1 in AP-1-dependent Rta activation of BZLF1 transcription.
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Ya-Yun
authors.initials: YY
authors.lastname: Chu
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Ya-Chun
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Molecular Genetics Laboratory, Department of Microbiology and Immunology, Chang-Gung University, Taoyuan, Taiwan.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Hsu
authors.affiliation: Molecular Genetics Laboratory, Department of Microbiology and Immunology, Chang-Gung University, Taoyuan, Taiwan.
authors.forename: Shih-Tung
authors.initials: ST
authors.lastname: Liu
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Li-Kwan
authors.initials: LK
authors.lastname: Chang
mesh_terms: D051698:Activating Transcription Factor 2 / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D045744:Cell Line, Tumor; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation; D008562:Membrane Glycoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D012097:Repressor Proteins; D015534:Trans-Activators / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
chemical_list: C501309:ATF7IP protein, human; D051698:Activating Transcription Factor 2; C109482:BMRF-2 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D008562:Membrane Glycoproteins; D012097:Repressor Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014764:Viral Proteins