EBNA1, a nuclear protein expressed in all EBV-associated neoplasms is 
indispensable for the maintenance of the viral episomes in latently infected 
cells. EBNA1 may induce genetic alterations by upregulating cellular 
recombinases, production of reactive oxygen species (ROS) and affecting p53 
levels and function. All these changes may contribute to tumorigenesis. In this 
overview we focus, however, on the epigenetic alterations elicited by EBNA1 by 
drawing a parallel between EBNA1 and the FoxA family of pioneer transcription 
factors. Both EBNA1 and FoxA induce local DNA demethylation, nucleosome 
destabilization and bind to mitotic chromosomes. Local DNA demethylation and 
nucleosome rearrangement mark active promoters and enhancers. In addition, EBNA1 
and FoxA, when associated with mitotic chromatin may "bookmark" active genes and 
ensure their reactivation in postmitotic cells (epigenetic memory). We speculate 
that DNA looping induced by EBNA1-EBNA1 interactions may reorganize the cellular 
genome. Such chromatin loops, sustained in mitotic chromatin similarly to the 
long-distance interactions mediated by the insulator protein CTCF, may also 
mediate the epigenetic inheritance of gene expression patterns. We suggest that 
EBNA1 has the potential to induce patho-epigenetic alterations contributing to 
tumorigenesis.