The Epstein-Barr virus (EBV) protein, EBNA2, is essential for B cell immortalization which underlies the pathogenesis of EBV-related lymphomas in immunosuppressed patients. EBNA2 activates transcription of specific genes indirectly through its association with the ubiquitous DNA binding protein, CBF1/RBP-Jk. A fraction of phosphorylated EBNA2 is associated with hSNF5/Ini1 in EBV infected B cells. hSNF5 is a component of the human SWI/SNF chromatin remodeling complex. Using chromatin immunoprecipitation, SWI/SNF components hSNF5 and BRG1 are found associated with specific EBNA2-responsive elements on an episomal construct and the cellular CD23 gene. This is the first demonstration of recruitment of the hSWI/SNF complex in vivo. The mechanism of EBNA2-associated SWI/SNF function will be investigated. Critical amino acids in EBNA2 will be identified that mediate the interaction with hSNF5, and mutants which fail to bind hSNF5 will be tested for the ability to activated transcription, alter chromatin structure, and induce cellular transformation. Components of the EBNA2-hSNF5 complex will be identified, and the possible function of the repressor EBNA3C will be studied.
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