ArticleJournal of leukocyte biology2014
The double bromodomain protein Brd2 promotes B cell expansion and mitogenesis.
Article in Journal of leukocyte biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- Maternal dysglycaemia, changes in the infant's epigenome modified with a diet and physical activity intervention in pregnancy: Secondary analysis of a randomised control trial.PLoS medicine · 2020Trial
- Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population.Scientific reports · 2016Trial
- Transcription factors in the development and treatment of immune disorders.Transcription · 2025Review
- Bromodomain and extra-terminal proteins in solid tumors: regulators of immune microenvironment and emerging therapeutic targets.Frontiers in immunology · 2025Review
- Identification of Plasma Protein Biomarkers and Drug Targets for Hematologic Malignancies by Proteome-wide Mendelian Randomization.Journal of Cancer · 2025Article
- miR-143 promotes cell proliferation, invasion and migration via directly binding to BRD2 in lens epithelial cells.American journal of translational research · 2024Article
- Serum BRD2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide‑conjugated BSA.International journal of oncology · 2022Article
- Novel forms of prostate cancer chemoresistance to successful androgen deprivation therapy demand new approaches: Rationale for targeting BET proteins.The Prostate · 2022Review
- Host T Cell Dedifferentiation Effects Drive HIV-1 Latency Stability.Journal of virology · 2022Article
- Emerging Proteins in CRPC: Functional Roles and Clinical Implications.Frontiers in oncology · 2022Review
- Zebrafish ParalogsJournal of developmental biology · 2021Article
- Inhibitors of bromodomain and extra-terminal proteins for treating multiple human diseases.Medicinal research reviews · 2021Review
- The bromodomain and extra-terminal domain degrader MZ1 exhibits preclinical anti-tumoral activity in diffuse large B-cell lymphoma of the activated B cell-like type.Exploration of targeted anti-tumor therapy · 2021Article
- Article
- BRD4 Regulates Metastatic Potential of Castration-Resistant Prostate Cancer through AHNAK.Molecular cancer research : MCR · 2019Article
- Exploiting a water network to achieve enthalpy-driven, bromodomain-selective BET inhibitors.Bioorganic & medicinal chemistry · 2018Article
- Review: Enhancers in Autoimmune Arthritis: Implications and Therapeutic Potential.Arthritis & rheumatology (Hoboken, N.J.) · 2017Review
- Review
- Bromodomain protein Brd3 promotes Ifnb1 transcription via enhancing IRF3/p300 complex formation and recruitment to Ifnb1 promoter in macrophages.Scientific reports · 2017Article
- BET bromodomain proteins and epigenetic regulation of inflammation: implications for type 2 diabetes and breast cancer.Cellular and molecular life sciences : CMLS · 2017Review
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
Bromodomain-containing transcriptional regulators represent new epigenetic targets in different hematologic malignancies. However, bromodomain-mediated mechanisms that couple histone acetylation to transcription in lymphopoiesis and govern mature lymphocyte mitogenesis are poorly understood. Brd2, a transcriptional coregulator that contains dual bromodomains and an extraterminal domain (the BET family), couples chromatin to cell-cycle progression. We reported previously the first functional characterization of a BET protein as an effector of mammalian mitogenic signal transduction: Eμ-Brd2 Tg mice develop "activated B cell" diffuse large B cell lymphoma. No other animal models exist for genetic or lentiviral expression of BET proteins, hampering testing of novel anti-BET anticancer drugs, such as JQ1. We transduced HSCs with Brd2 lentivirus and reconstituted recipient mice to test the hypothesis that Brd2 regulates hematopoiesis in BM and mitogenesis in the periphery. Forced expression of Brd2 provides an expansion advantage to the donor-derived B cell compartment in BM and increases mature B cell mitogenic responsiveness in vitro. Brd2 binds the cyclin A promoter in B cells, shown by ChIP, and increases cyclin A mRNA and protein levels, and S-phase progression in vitro in mitogen-stimulated primary B cells, but not T cells, reinforcing results from Eμ-Brd2 mice. The small molecule BET inhibitor JQ1 reduces B cell mitogenesis, consistent with the interpretation that BET inhibitors are antiproliferative. Brd2-specific knockdown experiments show that Brd2 is also required for hematopoiesis. We conclude that Brd2 plays a critical, independent role in regulation of mitogenic response genes, particularly cyclin A, in B cells.
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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.