%0 Journal Article
%T EBNA2 Drives Formation of New Chromosome Binding Sites and Target Genes for B-Cell Master Regulatory Transcription Factors RBP-j百 and EBF1
%A Fang Lu&nbsp
%A Horng-Shen Chen&nbsp
%A Andrew V. Kossenkov&nbsp
%A Karen DeWispeleare&nbsp
%A Kyoung-Jae Won&nbsp
%A Paul M. Lieberman
%J PLOS Pathogens
%D 2016
%I Public Library of Science (PLoS)
%R 10.1371/journal.ppat.1005339
%X Epstein-Barr Virus (EBV) transforms resting B-lymphocytes into proliferating lymphoblasts to establish latent infections that can give rise to malignancies. We show here that EBV-encoded transcriptional regulator EBNA2 drives the cooperative and combinatorial genome-wide binding of two master regulators of B-cell fate, namely EBF1 and RBP-j百. Previous studies suggest that these B-cell factors are statically bound to target gene promoters. In contrast, we found that EBNA2 induces the formation of new binding for both RBP-j百 and EBF1, many of which are in close physical proximity in the cellular and viral genome. These newly induced binding sites co-occupied by EBNA2-EBF1-RBP-j百 correlate strongly with transcriptional activation of linked genes that are important for B-lymphoblast function. Conditional expression or repression of EBNA2 leads to a rapid alteration in RBP-j百 and EBF1 binding. Biochemical and shRNA depletion studies provide evidence for cooperative assembly at co-occupied sites. These findings reveal that EBNA2 facilitate combinatorial interactions to induce new patterns of transcription factor occupancy and gene programming necessary to drive B-lymphoblast growth and survival.
%U http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1005339