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

Abstract

Histone acetylation alters the chromatin structure and activates the genes that are repressed by histone deacetylation. This investigation demonstrates 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 and 12-O:-tetradecanoylphorbol-13-acetate synergistically activate the transcription of BRLF1, an immediate-early gene of EBV. Chromatin immunoprecipitation assay reveals that histone H4 at the BRLF1 promoter is acetylated after P3HR1 cells are treated with TSA, suggesting that histone acetylation activates BRLF1 transcription. Furthermore, results in this study demonstrate that mutation of a YY1-binding site in the BRLF1 promoter activates BRLF1 transcription 1.6- and 2.3-fold in P3HR1 cells and C33A cells, respectively. Real time PCR analysis reveals that the mutation also increases the histone acetylation level of the nucleosomes at the BRLF1 promoter 1. 64- and 3.08-fold in P3HR1 and C33A cells, respectively. Results presented herein suggest that histone deacetylation plays an important role in maintaining the viral latency and histone acetylation at the BRLF1 promoter allows the virus to express Rta and to activate the viral lytic cycle.

Lactogenic Hormonal Induction of Long Distance Interactions between β-Casein Gene Regulatory Elements

“…However, ChIP assays using antibodies to HDAC1 did not reveal a correlation of HDAC1 association with the dynamics of YY-1 disassociation at the proximal promoter (2). These data are consistent with results demonstrating that the YY-1-HDAC1 complex was not supershifted by HDAC1 antibodies (7) and suggest that a histone deacetylase other than HDAC1 is most likely associated with YY-1 resulting in transcriptional repression. One possible candidate could be HDAC3 that possesses histone deacetylase activity, represses transcription when tethered to a promoter, and binds the YY-1 transcription factor (8).…”

Retracted: Transactivation of the CCL5/RANTES gene by Epstein‐Barr virus latent membrane protein 1

“…37,38 HDACI exposure results in induction of LMP-1 in an EBV-positive BL cell line. 39 Therefore, we determined whether HDACI (FR90028) treatment induced endogenous LMP-1 transcripts in Daudi cells.…”

Protein Kinase C-Independent Activation of the Epstein-Barr Virus Lytic Cycle

“…A number of different stimuli have been shown to trigger the switch into the lytic cycle. These include halogenated pyrimidines (25), nutrient starvation (27), phorbol esters (61), calcium ionophores (16), transforming growth factor ␤1 (17), n-butyrate (36), specific histone deacetylase (HDAC) inhibitors such as trichostatin A (TSA) (9,29), the demethylating agent azacytidine (5), cross-linking of surface immunoglobulin (53), superinfection with EBV stocks containing rearranged defective DNA (41,43), and superinfection with human herpesvirus 6 (21). A general unanswered question is whether all inducing agents operate through a final common pathway.…”