Journal
VIROLOGY
Volume 397, Issue 2, Pages 299-310Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2009.11.023
Keywords
Epstein-Barr virus; EBV; Nuclear antigen 2; EBNA2; Methylation; Arginine; sDMA; aDMA; RBPJ kappa; DNA-binding
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [KR2218/2-1, GR950/12-1]
- Wellcome Trust [078291]
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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 RBPJ kappa (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 RBPJ kappa 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 RBPJ kappa. (C) 2009 Elsevier Inc. All rights reserved.
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