ArticlePLoS pathogens2011
RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Review
- Chromatin Control of EBV Infection and Latency.Current topics in microbiology and immunology · 2025Article
- BET activity plays an essential role in control of stem cell attributes in Xenopus.Development (Cambridge, England) · 2024Article
- An alpha-herpesvirus employs host HEXIM1 to promote viral transcription.Journal of virology · 2024Article
- The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC.Nucleic acids research · 2023Article
- Reactivation of Epstein-Barr Virus from Latency Involves Increased RNA Polymerase Activity at CTCF Binding Sites on the Viral Genome.Journal of virology · 2023Article
- P-TEFb as A Promising Therapeutic Target.Molecules (Basel, Switzerland) · 2020Review
- Bromodomain Inhibitors as Therapeutics for Herpesvirus-Related Disease: All BETs Are Off?Frontiers in cellular and infection microbiology · 2020Review
- Cyclin-dependent kinase 9 as a potential specific molecular target in NK-cell leukemia/lymphoma.Haematologica · 2018Article
- BET bromodomain inhibitors show anti-papillomavirus activity in vitro and block CRPV wart growth in vivo.Antiviral research · 2018Article
- Epstein-Barr virus nuclear antigen EBNA-LP is essential for transforming naïve B cells, and facilitates recruitment of transcription factors to the viral genome.PLoS pathogens · 2018Article
- Bromodomain and extraterminal inhibitors block the Epstein-Barr virus lytic cycle at two distinct steps.The Journal of biological chemistry · 2017Article
- Regulation of the human papillomavirus type 16 late promoter by transcriptional elongation.Virology · 2017Article
- Review
- A Novel Bromodomain Inhibitor Reverses HIV-1 Latency through Specific Binding with BRD4 to Promote Tat and P-TEFb Association.Frontiers in microbiology · 2017Article
- RUNX super-enhancer control through the Notch pathway by Epstein-Barr virus transcription factors regulates B cell growth.Nucleic acids research · 2016Article
- P-TEFb goes viral.Inside the cell · 2016Review
- Therapeutics Targeting Protein Acetylation Perturb Latency of Human Viruses.ACS chemical biology · 2016Review
- Papillomavirus-Associated Tumor Formation Critically Depends on c-Fos Expression Induced by Viral Protein E2 and Bromodomain Protein Brd4.PLoS pathogens · 2016Article
- Infection by Herpes Simplex Virus 1 Causes Near-Complete Loss of RNA Polymerase II Occupancy on the Host Cell Genome.Journal of virology · 2015Article
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3 authors.
Funding
Abstract
Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions.
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