EBV Conference 2008 Guangzhou - Baylor College of Medicine

83 (RegID: 1708; 1710; 1711)
Ingemar Ernberg
Institution: Karolinska Institutet
e-mail: ingemar.ernberg@ki.se
OCT2 AND EBNA 1 IN THE CONTROL OF SWITCHING BETWEEN LATENCY PROGRAMS
Zou, J., Werner, M. , Aurell, E., Borestrom, C., Almqvist, J., Rymo, L., Ernberg,I
Department of Microbiology, Tumor and Cell Biology, MTC, Karolinska Institute, Stockholm Sweden;
1) Theoretical Biological Physics, Dept of Physics, Royal Shool of Technology, Stockholm,Sweden; 2)
Department of Clinical Chemistry and Transfusion Medicine Sahlgrenska University Hospital Goteburg
Sweden;
Posterabstract:
The switch between latancy programs I/II and III EBV have major implications for cell cycle entry and
exit, and thus for viral pathogenesis. The family of repeats (FR) is the major upstream control element of
the EBV latent C promoter (Cp), driving latency III and cell proliferation. It can be activated by the
binding of multiple EBV nuclear protein EBNA1s. We have earlier shown that OCT-transcription factors
also can bind to and activate FR, as demonstrated by electrophoretic mobility shift assay (EMSA), by an
affinity DNA-binding assay (“DNA-fishing”), chromatine immuno precipitation (ChIP) and luciferase
based reporter assays. We have also shown that OCT proteins turned into repressors by Grg/TLE can
repress promoter activity through EBVs FR. We have knocked down Oct2 levels in latency I cells, which
affects EBNA1 expression levels. A mechanical statistical model has been developed for this switch and
its control by EBNA1 and Oct2. From the model can be inferred the key regulatory events and numbers of
molecules required for the switch to occur. With this model we propose one mechanism for switching
between EBV driven cell cycle entry or exit, as consequencies of the latency program switches.
EBV Conference 2008 Guangzhou
- 143 -