Activation of the BRLF1 promoter and lytic cycle of Epstein-Barr virus by histone acetylation

Histone acetylation alters the chromatin structure and activates the genes that are repressed by histone deacetylation. This investigation demonstrate s that treating P3HR1 cells with trichostatin A (TSA) activates the Epstein -Barr virus (EBV) lytic cycle, allowing the virus to synthesize three viral lytic proteins-Rta, Zta and EA-D. Experimental results indicate that TSA a nd 12-O-tetradecanoylphorbol-13-acetate synergistically activate the transc ription of BRLF1, an immediate-early gene of EBV. Chromatin immunoprecipita tion assay reveals that histone H4 at the BRLF1 promoter is acetylated afte r P3HR1 cells are treated with TSA, suggesting that histone acetylation act ivates BRLF1 transcription. Furthermore, results in this study demonstrate that mutation of a YY1-binding site in the BRLF1 promoter activates BRLF1 t ranscription 1.6- and 2.3-fold in P3HR1 cells and C33A cells, respectively. Real time PCR analysis reveals that the mutation also increases the histon e acetylation level of the nucleosomes at the BRLF1 promoter 1.64- and 3.08 -fold in P3HR1 and C33A cells, respectively. Results presented herein sugge st that histone deacetylation plays an important role in maintaining the vi ral latency and histone acetylation at the BRLF1. promoter allows the virus to express Rta and to activate the viral lytic cycle.