Asymmetric Arginine dimethylation of Epstein–Barr virus nuclear antigen 2 promotes DNA targeting

Gross, Henrik, Barth, Stephanie, Palermo, Richard D, Mamiani, Alfredo, Hennard, Christine, Zimber-Strobl, Ursula, West, Michelle J, Kremmer, Elisabeth and Grasser, Friedrich A (2010) Asymmetric Arginine dimethylation of Epstein–Barr virus nuclear antigen 2 promotes DNA targeting. Virology, 397 (2). pp. 299-310. ISSN 0042-6822

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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 RBPJk (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 RBPJk 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 RBPJk.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Richard Palermo
Date Deposited: 06 Feb 2012 20:38
Last Modified: 22 Mar 2012 14:28
URI: http://sro.sussex.ac.uk/id/eprint/27155
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