EBNA1-DNA Interactions

Abstract

Soon after EBNA1 was found to be required to replicate and maintain oriP plasmids, EBNA1 was shown to bind to specific sequences in the oriP FR and DS elements through its C-terminal region (Jones et al. 1989; Rawlins et al. 1985). A screen for EBV genomic fragments bound by EBNA1 not only identified the FR and DS elements but also a fragment referred to as BamHI-Q (Jones et al. 1989), which was later shown to contain a promoter (Qp) used for the expression of EBNA1 in the absence of other EBNAs (Jones et al. 1989; Nonkwelo et al. 1996; Sample et al. 1992). EBNA1 was shown to have the highest affinity for the FR region, followed by the DS then the BamHI-Q region (Jones et al. 1989). All of the EBNA1-bound EBV fragments contained multiple copies of an 18 bp palindromic sequence that was protected by EBNA1 (Ambinder et al. 1990; Rawlins et al. 1985). The multiple copies of this sequence in the EBV genome are not identical but contain some variations that account for the different affinities of EBNA1 for the FR, DS and BamHI-Q regions and for individual sites within these regions (Ambinder et al. 1990; Summers et al. 1996). The BamHI-Q region contains two EBNA1 recognition sites that decrease EBNA1 expression when bound by EBNA1, enabling EBNA1 to autoregulate its own expression (Ambinder et al. 1990; Jones et al. 1989; Yoshioka et al. 2008).