title: Asymmetric Arginine dimethylation of Epstein-Barr virus nuclear antigen 2 promotes DNA targeting.
abstract: The Epstein-Barr virus (EBV) growth-transforms B-lymphocytes. The virus-encoded nuclear antigen 2 (EBNA2) is essential for transformation and activates gene expression by association with DNA-bound transcription factors such as RBPJkappa (CSL/CBF1). We have previously shown that EBNA2 contains symmetrically dimethylated Arginine (sDMA) residues. Deletion of the RG-repeat results in a reduced ability of the virus to immortalise B-cells. We now show that the RG repeat also contains asymmetrically dimethylated Arginines (aDMA) but neither non-methylated (NMA) Arginines nor citrulline residues. We demonstrate that only aDMA-containing EBNA2 is found in a complex with DNA-bound RBPJkappa in vitro and preferentially associates with the EBNA2-responsive EBV C, LMP1 and LMP2A promoters in vivo. Inhibition of methylation in EBV-infected cells results in reduced expression of the EBNA2-regulated viral gene LMP1, providing additional evidence that methylation is a prerequisite for DNA-binding by EBNA2 via association with the transcription factor RBPJkappa.
authors.affiliation: Institut für Virologie, Haus 47, Universitätsklinikum, 66421 Homburg/Saar, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Gross
authors.forename: Stephanie
authors.initials: S
authors.lastname: Barth
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palermo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mamiani
authors.forename: Christine
authors.initials: C
authors.lastname: Hennard
authors.forename: Ursula
authors.initials: U
authors.lastname: Zimber-Strobl
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: West
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Friedrich A
authors.initials: FA
authors.lastname: Grässer
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D014763:Viral Matrix Proteins / Q000096:biosynthesis; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497570:RBPJ protein, human; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D004247:DNA; D001120:Arginine