Epstein-Barr Virus Nuclear Antigen 3C binds to BATF/IRF4 or SPI1/IRF4 composite sites and recruits Sin3A to repress CDKN2A
Abstract
Epstein-Barr virus (EBV) is an important causative agent of B-cell lymphomas and Hodgkin disease in immune-deficient people, including HIV-infected people. The experiments described here were undertaken to determine the mechanisms through which the EBV-encoded nuclear protein EBNA3C blocks the cell p14ARF and p16INK4A tumor suppressor-mediated inhibition of EBV-infected B-cell growth, thereby unfettering EBV-driven B-cell proliferation. The experiments also identify the molecular basis for diverse EBNA3C enhancer interactions with cell DNA-binding proteins and cell DNA to regulate MYC, pRB, BCL2, and BIM expression. Surprisingly, EBNA3C's role in enhancer-mediated cell gene transcription up-regulation is primarily mediated by combinatorial effects with cell transcription factors, most notably AICEs, EICEs, and RUNX3.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- January 2014
- DOI:
- 10.1073/pnas.1321704111
- Bibcode:
- 2014PNAS..111..421J