ArticleThe Journal of biological chemistry2009
Chromatin adaptor Brd4 modulates E2 transcription activity and protein stability.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 75 citations in OpenAlex.
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Pharmacological targeting of oncogenic condensates in cancer: mechanistic insights and therapeutic opportunities.Acta pharmacologica Sinica · 2026Review
- E2 Tyrosine 102 Regulates MmuPV1 Pathogenesis In Vivo.Pathogens (Basel, Switzerland) · 2025Article
- A Conserved Di-Lysine Motif in the E2 Transactivation Domain Regulates MmuPV1 Replication and Disease Progression.Pathogens (Basel, Switzerland) · 2025Article
- Senataxin mediates R-loop resolution on HPV episomes.Journal of virology · 2024Article
- IDR-targeting compounds suppress HPV genome replication via disruption of phospho-BRD4 association with DNA damage response factors.Molecular cell · 2024Article
- SETD6 Regulates E2-Dependent Human Papillomavirus Transcription.Journal of virology · 2022Article
- Relevance of BET Family Proteins in SARS-CoV-2 Infection.Biomolecules · 2021Review
- BRD4S interacts with viral E2 protein to limit human papillomavirus late transcription.Journal of virology · 2021Article
- Multiple Roles of Brd4 in the Infectious Cycle of Human Papillomaviruses.Frontiers in molecular biosciences · 2021Review
- Phosphorylation of the Human Papillomavirus E2 Protein at Tyrosine 138 Regulates Episomal Replication.Journal of virology · 2020Article
- Opposing Functions of BRD4 Isoforms in Breast Cancer.Molecular cell · 2020Article
- Phosphorylation of a Conserved Tyrosine in the Papillomavirus E2 Protein Regulates Brd4 Binding and Viral Replication.Journal of virology · 2019Article
- Cottontail Rabbit Papillomavirus E1 and E2 Proteins Mutually Influence Their Subcellular Localizations.Journal of virology · 2018Article
- BET bromodomain inhibitors show anti-papillomavirus activity in vitro and block CRPV wart growth in vivo.Antiviral research · 2018Article
- Bromodomain proteins GTE9 and GTE11 are essential for specific BT2-mediated sugar and ABA responses in Arabidopsis thaliana.Plant molecular biology · 2018Article
- Human Papillomavirus Replication Regulation by Acetylation of a Conserved Lysine in the E2 Protein.Journal of virology · 2018Article
- Involvement of Brd4 in different steps of the papillomavirus life cycle.Virus research · 2017Review
- Phosphorylation of the Bovine Papillomavirus E2 Protein on Tyrosine Regulates Its Transcription and Replication Functions.Journal of virology · 2017Article
- BRD4 Phosphorylation Regulates HPV E2-Mediated Viral Transcription, Origin Replication, and Cellular MMP-9 Expression.Cell reports · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Brd4 is a chromatin adaptor containing tandem bromodomains binding to acetylated histone H3 and H4. Although Brd4 has been implicated in the transcriptional control of papillomavirus-encoded E2 protein, it is unclear how Brd4 regulates E2 function and whether the involvement of Brd4 in transactivation and transrepression is common to different types of E2 proteins. Using DNase I footprinting performed with in vitro reconstituted human papillomavirus (HPV) chromatin and nucleosome-free DNA templates, we found that Brd4 facilitates E2 binding to its cognate sequences in chromatin depending on bromodomains and the E2-interacting region of Brd4. Moreover, the coactivator and corepressor function of Brd4 requires at least one intact bromodomain and is mediated by its direct association with E2 proteins encoded by cancer-inducing high risk HPV-16 and HPV-18, wart-causing low risk HPV-11, and bovine papillomavirus type 1, in part through enhancing the protein stability of E2 that is normally degraded via the ubiquitin-dependent proteasome pathway. Our findings indicate that a chromatin adaptor can bridge and enhance the binding of a sequence-specific transcription factor to chromatin and further promote the stability of a labile transcription factor via direct protein-protein interaction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.