Affinage

BRD2

Bromodomain-containing protein 2 · UniProt P25440

Length
801 aa
Mass
88.1 kDa
Annotated
2026-06-09
100 papers in source corpus 42 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BRD2 is a BET-family double-bromodomain protein that reads acetylated histone H4 and acts as a chromatin-associated transcriptional scaffold and architectural factor (PMID:18406326, PMID:17148447). Its N-terminal bromodomain forms a homodimer with two acetyllysine-binding pockets that specifically recognizes H4 acetylated at Lys12, with hypoacetylated Lys8 binding at the dimer interface to complete recognition (PMID:17148447, PMID:20048151). BRD2 associates along the entire lengths of transcribed genes enriched in H4K5ac/H4K12ac/H3K14ac and enables RNA Pol II to transcribe through nucleosomes in a defined in vitro system, with intrinsic histone chaperone activity (PMID:18406326); chromatin recruitment also depends on features of the histone variant H2A.Z and is antagonized by H2A.Z.1 monoubiquitylation at bivalent promoters (PMID:23144632, PMID:26804911). Mechanistically, BRD2 recruits E2F-1/E2F-2 and H4-directed acetyltransferase activity together with TBP to E2F-responsive promoters such as cyclin A to promote cell-cycle gene transcription (PMID:10965846, PMID:15548137, PMID:17111193), and it supports RNA Pol II initiation through TAF3 at promoters with low H3K4me3 while suppressing R-loops during elongation (PMID:35665862). Independently of transcriptional readout, BRD2 co-localizes genome-wide with the insulator protein CTCF, which recruits it to enforce topological domain boundaries, and it promotes A/B compartmentalization of active chromatin via its double bromodomain and low-complexity domain in an interplay with cohesin and BRD4 (PMID:28388437, PMID:35410381). BRD2 is required for embryogenesis and neural tube closure, acting upstream of E2F1 to control cell-cycle exit and neuronal differentiation (PMID:19301389, PMID:19362612, PMID:22885183). Context-specific roles include macrophage inflammatory cytokine gene activation (PMID:23420887), STAT5-dependent leukemic transcription (PMID:24435449), Th17 enhancer assembly through CTCF/cohesin and acetylation-sensitive Stat3 binding (PMID:28262505), ACE2 and interferon-stimulated gene regulation (PMID:35027731, PMID:30240626), recruitment to DNA double-strand breaks where it protects Tip60-generated H4Ac and modulates 53BP1/ZMYND8 (PMID:29018219), and metabolic gene control in adipocytes and pancreatic β-cells (PMID:19883376). BRD2 protein stability is governed by SPOP-mediated ubiquitination, which phosphocreatine antagonizes by outcompeting SPOP binding (PMID:38563585).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 High

    Established that RING3/BRD2 functions as a nuclear transcriptional activator of cell-cycle genes coupled to E2F and the Rb/Ras axis, defining its earliest mechanistic role.

    Evidence reporter transactivation, kinase-dead mutagenesis, E2F co-purification and Rb epistasis; NLS mutagenesis with serum-induced nuclear translocation

    PMID:10934046 PMID:10965846

    Open questions at the time
    • Whether transactivation requires a genuine intrinsic kinase activity was not resolved structurally
    • Direct versus scaffold-mediated E2F engagement not distinguished
  2. 2005 High

    Showed that BRD2 physically occupies the cyclin A promoter and delivers E2F-1 and H4-acetyltransferase activity, converting the genetic link into a chromatin-recruitment mechanism.

    Evidence ChIP at cyclin A promoter, Co-IP, HAT assays in immunopurified complexes, cell-cycle analysis

    PMID:15548137

    Open questions at the time
    • Identity of the associated acetyltransferase not defined in this study
    • Direct contact surface with E2F not mapped
  3. 2006 High

    Resolved the structural basis of acetyllysine reading: BD1 is a homodimer that specifically binds H4K12ac, and BRD2 bridges to the basal machinery via TBP.

    Evidence X-ray crystallography of BD1, dimerization assays, reciprocal Co-IP and peptide mapping of BRD2-TBP interaction

    PMID:17111193 PMID:17148447

    Open questions at the time
    • Physiological consequence of BD1 dimerization on full-length chromatin binding not addressed
    • Generality of TBP recruitment beyond E2F promoters unknown
  4. 2008 High

    Defined the genome-wide chromatin behavior and biochemical readout: BRD2 tracks hyperacetylated transcribed gene bodies and supports Pol II transcription through nucleosomes.

    Evidence ChIP-seq, defined in vitro transcription reconstitution, histone modification analysis

    PMID:18406326

    Open questions at the time
    • Mechanism of intrinsic histone chaperone activity not structurally defined
    • Functional separation of BRD2 from BRD3 in vivo not established here
  5. 2009 High

    Demonstrated an essential, embryo-autonomous developmental requirement and connected BRD2's cell-cycle function to neural fate via E2F1.

    Evidence knockout mice with tetraploid complementation, in situ hybridization; later double-mutant E2F1 rescue and metabolic knockout phenotyping

    PMID:19301389 PMID:19362612 PMID:19883376 PMID:22885183

    Open questions at the time
    • Tissue-specific transcriptional targets driving neural tube closure not enumerated
    • Molecular link between BRD2 loss and metabolic phenotypes incomplete
  6. 2012 Medium

    Extended chromatin recruitment beyond H4ac to the histone variant H2A.Z, showing combinatorial targeting that controls specific gene programs.

    Evidence nucleosome purification/MS, Co-IP, ChIP, chemical inhibition; H2A.Z.1 monoubiquitylation mutant ESCs with BRD2 ChIP and inhibitor rescue

    PMID:23144632 PMID:26804911

    Open questions at the time
    • Direct H2A.Z recognition surface on BRD2 not identified
    • How monoubiquitylation sterically antagonizes BRD2 binding not resolved
  7. 2013 High

    Mapped functional domain contributions and broadened BRD2's output to alternative splicing and inflammatory cytokine gene activation in macrophages.

    Evidence FRAP with domain deletions, transcriptome screen, Co-IP; ChIP at cytokine promoters with genetic hypomorph, siRNA and JQ1

    PMID:23420887 PMID:24048450 PMID:24319289

    Open questions at the time
    • Splicing regulation mechanism (co-transcriptional vs. spliceosome contact) undefined
    • C-terminal domain binding partners not identified
  8. 2017 High

    Revealed a non-transcriptional architectural role: BRD2 is recruited by CTCF to enforce topological boundaries and prevent regulatory cross-talk, distinguishing it from BRD4.

    Evidence ChIP-seq, Hi-C, single-molecule FISH with BRD2 depletion and CTCF disruption; Th17 enhancer assembly with cohesin and Stat3

    PMID:28262505 PMID:28388437

    Open questions at the time
    • Whether BRD2 stabilizes CTCF/cohesin or acts as an independent insulator not fully separated
    • Direct CTCF-BRD2 contact surface not mapped
  9. 2017 Medium

    Implicated BRD2 in DNA double-strand break repair by reading Tip60-generated H4 acetylation to protect the mark and organize downstream repair factors.

    Evidence ChIP at laser-induced DSBs, bromodomain mutant rescue, ZMYND8/53BP1 co-localization

    PMID:29018219

    Open questions at the time
    • Single-lab study without independent replication
    • Quantitative impact on repair pathway choice not established
  10. 2022 High

    Unified BRD2's architectural function mechanistically, showing it drives active-compartment mixing through its double bromodomain and low-complexity domain in antagonism with cohesin/BRD4, and elevated its biomedical role to ACE2/ISG control.

    Evidence Hi-C after cohesin depletion, live imaging, domain mutagenesis, polymer simulation; CRISPRi/pharmacological ACE2 and SARS-CoV-2 in vitro and hamster model; auxin-degron ChIP-seq for TAF3/R-loop functions

    PMID:35027731 PMID:35410381 PMID:35665862

    Open questions at the time
    • How LCD-mediated partner binding integrates with bromodomain reading is not resolved at atomic level
    • Direct versus indirect control of the ACE2 promoter not fully dissected
  11. 2024 Medium

    Identified post-translational control of BRD2 abundance via SPOP-mediated ubiquitination antagonized by phosphocreatine, linking metabolism to BRD2-dependent gene expression.

    Evidence Co-IP of BRD2-SPOP, ubiquitination assays, cyclocreatine treatment, glioblastoma mouse models

    PMID:38563585

    Open questions at the time
    • Single-lab biochemistry without independent confirmation
    • SPOP degron within BRD2 not precisely mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BRD2 integrates acetyl-lysine reading, H2A.Z recognition, CTCF/cohesin association, and low-complexity-domain interactions into a single recruitment logic that selects between transcriptional, splicing, repair, and architectural outputs remains unresolved.
  • No structural model couples bromodomain reading to LCD-driven compartmentalization
  • Rules distinguishing BRD2-specific from BRD3/BRD4 target selection not established
  • Whether reported context-specific transcription-factor partnerships share a common recruitment mechanism is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 4 GO:0060090 molecular adaptor activity 4 GO:0140110 transcription regulator activity 4 GO:0044183 protein folding chaperone 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2 GO:0005730 nucleolus 1
Pathway
R-HSA-4839726 Chromatin organization 5 R-HSA-1640170 Cell Cycle 4 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-73894 DNA Repair 1
Partners
BRD7CTCFE2F1H2A.ZSPOPSTAT3STAT5TBP

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 BRD2 (and BRD3) associate preferentially with hyperacetylated chromatin along the entire lengths of transcribed genes, enriched in H4K5ac, H4K12ac, and H3K14ac marks, and allow RNA polymerase II to transcribe through nucleosomes in a defined in vitro transcription system dependent on specific histone H4 modifications. BRD2 also has intrinsic histone chaperone activity. ChIP-seq, defined in vitro transcription reconstitution assay, histone modification analysis Molecular cell High 18406326
2006 Crystal structure of the N-terminal bromodomain (BD1) of human BRD2 reveals a homodimer in solution and in the crystal, with two acetyllysine-binding pockets and a negatively charged secondary pocket at the dimer interface; BRD2 BD1 specifically recognizes histone H4 tail acetylated at Lys12 (H4K12ac). X-ray crystallography, biochemical dimerization assays The Journal of biological chemistry High 17148447
2010 Crystal structures of BRD2 BD1 in complex with three different H4K12ac peptides show that BD1 recognizes the H4 tail acetylated at Lys12, while hypoacetylated Lys8 of H4 binds at the dimer interface cavity; mutation of Lys8 in the H4K12ac peptide decreases binding to BRD2 BD1, establishing Lys8 as critical for recognition. X-ray crystallography, binding/mutagenesis studies The Journal of biological chemistry High 20048151
2000 RING3/BRD2 is a nuclear serine-threonine kinase that transactivates promoters of cell cycle regulatory genes (cyclin D1, cyclin A, cyclin E, DHFR) dependent on E2F binding sites and Ras signaling; a kinase-deficient point mutant fails to transactivate; nuclear extracts co-purify E2F-1 and E2F-2 with RING3 by immunoaffinity and recombinant protein affinity chromatography; Rb overexpression suppresses RING3-dependent transactivation. Transient transfection reporter assays, kinase-dead mutagenesis, immunoaffinity chromatography, epistasis with Rb overexpression Cell growth & differentiation High 10965846
2000 RING3/BRD2 is constitutively nuclear in proliferating HeLa cells but is delocalized in serum-starved fibroblasts and undergoes activation-induced nuclear translocation upon serum stimulation; site-directed mutagenesis of a monopartite classical nuclear localization sequence abolishes both nuclear translocation and transcriptional activity at E2F-dependent promoters. Immunostaining, confocal microscopy, site-directed mutagenesis of NLS, reporter transactivation assays Journal of cell science High 10934046
1999 RING3/BRD2 (ET domain) physically interacts with KSHV latent nuclear antigen (LANA); this interaction results in phosphorylation of serine/threonine residues in the C-terminal region of LANA (aa 951–1107); RING3 is not itself a kinase but recruits an unidentified serine/threonine kinase into the complex. Yeast two-hybrid, co-immunoprecipitation, deletion mapping, phosphorylation assay Journal of virology Medium 10559289
2005 BRD2 mediates recruitment of E2F-1/E2F-2 and histone H4-directed acetyltransferase activity to the cyclin A promoter in S-phase; ChIP shows BRD2 physically occupies the cyclin A promoter and its overexpression increases H4 acetylation at that promoter; BRD2-containing complexes contain E2F-1 and histone H4 acetyltransferase activity. Chromatin immunoprecipitation (ChIP), co-immunoprecipitation, histone acetyltransferase assay, overexpression/cell cycle analysis The Biochemical journal High 15548137
2006 BRD2 is a TBP-associated protein; the first bromodomain contains a 26 amino acid peptide essential for BRD2-TBP interaction; serum stimulation induces formation of a BRD2-E2F-1-TBP ternary complex, with BRD2 required for TBP recruitment to E2F-1-responsive promoters. Co-immunoprecipitation, deletion/peptide mapping, luciferase reporter assays, overexpression Molecular and cellular biochemistry Medium 17111193
2003 Lymphoid-restricted overexpression of BRD2 in Eμ-BRD2 transgenic mice drives B-cell lymphoma with increased cyclin A transcription; both wild-type and kinase-null BRD2 transgenes produce lymphomagenesis, indicating kinase activity is dispensable but BRD2-mediated recruitment of E2F factors and histone acetyltransferase to the cyclin A promoter is the mechanistic basis. Transgenic mouse model, kinase-dead mutant transgene, cyclin A transcription analysis Blood Medium 14563639
2009 Brd2 is required for embryogenesis and neural tube closure; homozygous Brd2-null embryos die by E11.5 with neural tube defects and exencephaly; Brd2 is highly expressed in the developing neural tube; Brd2-deficient embryos cannot be rescued by wild-type extraembryonic tissues, indicating an embryo-autonomous requirement. Knockout mouse generation, tetraploid complementation, in situ hybridization, cell proliferation assays Developmental dynamics / Biochimica et biophysica acta High 19301389 19362612
2012 Brd2 is required for cell cycle exit and neuronal differentiation in neuroepithelial cells; Brd2 deficiency accelerates cell cycle progression and impairs differentiation; genetic removal of E2F1 in Brd2-deficient mice rescues the neuronal differentiation and cell cycle abnormalities, placing Brd2 upstream of E2F1 in neuronal development. Transgene-insertion knockout, Brd2;E2F1 double-mutant genetic epistasis, cell cycle and differentiation marker analysis Biochemical and biophysical research communications High 22885183
2012 Brd2 is recruited to chromatin through a combination of hyperacetylated H4 (via its bromodomains) and additional features of the histone variant H2A.Z; Brd2 co-purifies preferentially with H2A.Z-containing nucleosomes and is required for androgen receptor (AR)-regulated gene expression in an H2A.Z-dependent manner. Nucleosome purification/mass spectrometry, co-immunoprecipitation, ChIP, chemical inhibition with cell-based reporter PLoS genetics Medium 23144632
2013 BRD2 and BRD4 physically associate with the promoters of inflammatory cytokine genes (e.g., IL-6, TNF-α) in macrophages; Brd2 hypomorphic mice show impaired proinflammatory cytokine production; siRNA knockdown and the BET inhibitor JQ1 independently abrogate macrophage inflammatory responses. ChIP, genetic hypomorph model, siRNA knockdown, small-molecule inhibitor (JQ1), in vivo LPS challenge Journal of immunology High 23420887
2013 The C-terminal domain of Brd2 is required for chromatin association; bromodomains and the C-terminal domain contribute equally to transcription and alternative splicing regulation; Brd2 regulates ~1450 genes transcriptionally and ~290 genes at the level of alternative splicing; live-cell FRAP imaging quantified Brd2 domain contributions to chromatin binding kinetics. Genome-wide screen (transcriptome), siRNA depletion, FRAP live-cell imaging, co-immunoprecipitation, domain deletion analysis Molecular biology of the cell Medium 24048450
2017 BRD2 co-localizes genome-wide with the architectural protein CTCF; CTCF recruits BRD2 to co-bound sites (BRD2 dispensable for CTCF occupancy); BRD2 depletion weakens topological domain boundaries co-occupied by CTCF and BRD2 (Hi-C), and allows regulatory influence to spread between adjacent genes (single-molecule FISH); BRD4 does not co-localize with CTCF. ChIP-seq, Hi-C, single-molecule mRNA FISH, BRD2 depletion, site-specific CTCF disruption Molecular cell High 28388437
2017 Brd2 associates with the chromatin insulator CTCF and the cohesin complex to support cis-regulatory enhancer assembly during Th17 cell differentiation; Brd2 binds the transcription factor Stat3 in an acetylation-sensitive manner and facilitates Stat3 recruitment to active enhancers occupied by Irf4 and Batf; Brd4 controls RNA Pol II processivity via cyclin T1/Cdk9 recruitment and Pol II Ser2 phosphorylation—distinct from Brd2's role. ChIP-seq, Co-IP (acetylation-sensitive), Th17 differentiation model with genetic depletion, Pol II Ser2 phosphorylation assay Molecular cell High 28262505
2022 BRD2 promotes spatial mixing and A/B compartmentalization of active chromatin after cohesin loss; this activity requires BRD2's double bromodomain (acetylated target recognition) and its low-complexity domain (binding partners); BRD4 and cohesin antagonize BRD2 binding to chromatin; polymer simulation supports a BRD2-cohesin interplay model for nuclear topology. Hi-C (cohesin depletion), live-cell imaging, domain mutant analysis, polymer simulation, ChIP-seq Nature genetics High 35410381
2016 H2A.Z.1 monoubiquitylation (H2A.Z.1ub) antagonizes BRD2 at bivalent gene promoters in ESCs; loss of monoubiquitylation results in BRD2 gain at de-repressed promoters, and BRD2 inhibition restores gene silencing at these sites, establishing an antagonistic relationship between H2A.Z.1ub and BRD2 in regulating transcriptional balance at bivalent genes. H2A.Z.1(K3R3) mutant ESCs, quantitative proteomics, BRD2 ChIP, BRD2 inhibitor rescue experiments Cell reports High 26804911
2017 BRD2 is spatially recruited to DNA double-strand breaks (DSBs) via its tandem bromodomains binding to H4 acetylation generated by Tip60/KAT5; BRD2 binding protects H4Ac from deacetylases and allows acetylation to spread ~2 kb flanking the DSB; BRD2 facilitates ZMYND8 recruitment to flanking chromatin, limits L3MBTL1 repressor binding, and promotes 53BP1 binding while limiting end-resection. ChIP at DSBs (laser damage), BRD2 domain mutant analysis, ZMYND8/53BP1 co-localization, bromodomain mutant rescue Scientific reports Medium 29018219
2018 HDAC11 suppresses the brown adipose tissue thermogenic program through physical association with BRD2; HDAC11 catalytic activity is required for this suppression and the mechanism depends on BRD2 interaction, as demonstrated by co-immunoprecipitation and cell-based assays. HDAC11 knockout mice, co-immunoprecipitation, cell-based transcriptional assays, ex vivo BAT analysis JCI insight Medium 30089714
2019 LYAR binds BRD2 through a mechanism not requiring acetyl-lysine-binding bromodomains and recruits BRD2 to rDNA promoters and transcribed regions via upstream binding factor (UBF); BRD2 is required for recruitment of the MYST-type acetyltransferase KAT7 to rDNA, resulting in enhanced local H4 acetylation and increased rRNA synthesis. Co-immunoprecipitation, ChIP-qPCR at rDNA, siRNA knockdown, histone acetylation analysis Nucleic acids research Medium 31504794
2022 BRD2 is required for ACE2 transcription in human lung epithelial cells and cardiomyocytes; BRD2 inhibition reduces endogenous ACE2 expression and blocks SARS-CoV-2 infection in human cells and Syrian hamsters; BRD2 also controls transcription of interferon-stimulated genes induced upon SARS-CoV-2 infection. Targeted CRISPRi screen, BRD2 pharmacological inhibition (ABBV-744), qRT-PCR, viral infection assay, in vivo hamster model Nature cell biology High 35027731
2014 BRD2 is the critical BET family mediator of STAT5 transcriptional activity; BRD2 knockdown (but not BRD3 or BRD4) selectively reduces STAT5-dependent (not STAT3-dependent) gene expression in leukemia cells; BRD2 knockdown synergizes with tyrosine kinase inhibitors in inducing apoptosis in STAT5-driven leukemia models. siRNA knockdown of individual BET proteins, STAT5 reporter assays, gene expression analysis, cell viability/apoptosis assays Molecular cancer therapeutics Medium 24435449
2009 Whole-body disruption of Brd2 causes severe obesity with pancreatic islet expansion and hyperinsulinemia but enhanced glucose tolerance; Brd2 normally inhibits beta-cell mitosis and insulin transcription; in adipocytes, Brd2 co-represses PPARγ and inhibits adipogenesis; Brd2 knockdown protects adipocytes from TNF-α-induced insulin resistance. Brd2 knockout mice, 3T3-L1 adipocyte knockdown, insulin secretion assay, metabolic phenotyping The Biochemical journal Medium 19883376
2013 BRD2 directly binds the cyclin A promoter in primary B cells (ChIP); forced Brd2 expression in B cells expands the B cell compartment and increases cyclin A mRNA/protein levels and S-phase progression in mitogen-stimulated B cells but not T cells; BRD2 is also required for hematopoiesis as shown by Brd2-specific knockdown. Lentiviral overexpression in HSCs with reconstitution, ChIP at cyclin A promoter, siRNA knockdown, cell cycle analysis Journal of leukocyte biology Medium 24319289
2013 A compound (1a) functions as a molecular glue degrader that drives interaction between BRD2/4 and the E3 ligase adaptor DCAF16 to promote BRD2/4 ubiquitination and degradation; CRISPR knockout of DCAF16 abolishes compound activity. CRISPR/Cas9 knockout screen of >1000 ligase genes, Co-IP of BRD2/4 with DCAF16, cellular degradation assays ACS chemical biology Medium 36656921
2013 NMR spectroscopy identified a specific binding site for the ET domains of BRD2 (and BRD4) on KSHV kLANA C-terminal domain; functional studies show oligomerization of kLANA CTD, the basic patch, and the ET binding site are all required for LANA nuclear speckle formation and latent replication. NMR spectroscopy, X-ray crystallography of LANA CTD, kLANA deletion/point mutants in functional replication and speckle assays PLoS pathogens High 24146614
2005 The C-terminal chromatin-binding domain of KSHV LANA-1 is required for interaction with Brd2/RING3, and this same domain is required for LANA-1 functions including binding and replication of viral episomal DNA, transcriptional modulation, and chromatin interaction; deletion mutant analysis maps the minimal interaction region. LANA-1 deletion mutants, Co-IP, episomal replication assay, transcription reporter assay Journal of virology Medium 16227282
2006 BRD2/RING3 (via ET domain) and BRD4S delay S-phase entry (G1 arrest) and increase cyclin E promoter activity when ectopically expressed; KSHV LANA-1 directly interacts with BRD4S C-terminal ET domain and partly releases cells from BRD4S- and BRD2/RING3-induced G1 arrest while reducing BRD4S-mediated cyclin E promoter activity. Ectopic expression in epithelial and B-cell lines, cell cycle FACS, cyclin E promoter reporter assay, Co-IP/domain mapping Journal of virology Medium 16928768
2018 BRD2 is required for IFN-stimulated H2A.Z eviction at ISG promoters; BRD2 (and GCN5) depletion blocks IFN-driven H2A.Z removal, impairs ISGF3 recruitment, and reduces ISG mRNA expression and antiviral immunity; BRD2 involvement is distinct from INO80 and SWI/SNF. siRNA knockdown of BRD2/GCN5/INO80/SWI-SNF, ChIP for H2A.Z and ISGF3, ISG mRNA quantification, viral infection assay iScience Medium 30240626
2020 BRD2 cooperates with acetylated ELK4 (acetylated at K125) to regulate LAMB3 transcription in colorectal cancer; ELK4 K125 acetylation enhances its interaction with BRD2; JQ1 disrupts ELK4-BRD2 interaction and reduces BRD2 binding to the LAMB3 promoter. Co-IP with acetylation mutants, ChIP at LAMB3 promoter, JQ1 treatment, mutagenesis of ELK4 K125 Oncogene Medium 32398865
2020 BRD2 silencing (but not BRD3 or BRD4) specifically averts sigma-2 receptor (S2R) up-regulation induced by cholesterol deprivation; endogenous BRD2 co-immunoprecipitates with the transcription-active N-terminal half of SREBP2; ChIP-qPCR shows co-occupancy of BRD2, H3K27ac, and SREBP2 at the S2R gene promoter, revealing a BRD2/SREBP2 cooperative transcriptional mechanism. Isoform-specific siRNA knockdown, Co-IP, ChIP-qPCR Life science alliance Medium 33234676
2022 BRD2 is required for TAF3-mediated RNA Pol II initiation at promoters with low H3K4me3 and for R-loop suppression during Pol II elongation; BRD2 and BRD3 function additively, independently, or antagonistically at different promoters; BRD2 also regulates genes critical for embryoid body differentiation by promoter priming in ESCs. Acute BRD2 protein degradation (auxin-inducible degron), ChIP-seq, quantitative proteomics, R-loop assay, BRD2/BRD3 single and double depletion Cellular and molecular life sciences High 35665862
2017 During pluripotent exit, Brd4 downregulation facilitates enhanced Brd2 occupancy at Nodal gene regulatory elements (NREs); Brd2 (not Brd4) is specifically required for differentiative Nodal-Smad2 signaling; BET proteins engage NREs to promote Nodal signaling and Smad2 developmental responses. Small-molecule screen, ChIP at NREs, targeted BRD2/BRD4 depletion, Smad2 activation assays EMBO reports Medium 28588073
2020 BRD2 promotes drug resistance in adult T-cell lymphoblastic lymphoma via the RasGRP1/Ras/ERK signaling pathway; BRD2 and E2F1 co-occupy the RasGRP1 promoter (ChIP), and BRD2 suppresses doxorubicin-induced apoptosis both in vitro and in vivo. ChIP at RasGRP1 promoter, Ras pull-down assay, overexpression/knockdown, xenograft model Cancer communications Medium 32459053
2024 Phosphocreatine (PCr) stabilizes BRD2 by inhibiting poly-ubiquitination; PCr outcompetes the E3 ubiquitin ligase SPOP for BRD2 binding, preventing SPOP-mediated BRD2 degradation; disruption of PCr biosynthesis by cyclocreatine leads to BRD2 degradation and decreased transcription of BRD2 target genes involved in chromosome segregation. Co-IP (BRD2-SPOP interaction), ubiquitination assay, cyclocreatine treatment, BRD2 stability assay, mouse GBM models Cancer discovery Medium 38563585
2013 Brd2 inhibits adipogenesis via the ERK1/2 signaling pathway; Brd2 overexpression increases ERK1/2 phosphorylation and represses PPARγ/C/EBPα expression; Brd2 knockdown decreases ERK1/2 activity independently of Raf signaling; MEK inhibitor UO126 partly restores adipogenic differentiation in Brd2-overexpressing cells. Overexpression and siRNA knockdown in 3T3-L1 cells, ERK1/2/JNK/p38 phosphorylation assays, MEK inhibitor epistasis PloS one Medium 24194944
2006 BRD2 physically interacts with BRD7 in mammalian cells; the region of BRD2 from amino acids 430–798 is critical for BRD2-BRD7 interaction; BRD2 localizes predominantly to the nucleus in diffuse and dotted patterns, with dotted distribution correlating with apoptosis. Co-immunoprecipitation, subcellular co-localization (GFP), deletion mapping, Hoechst staining Molecular and cellular biochemistry Low 16786191
2014 The growth factor pleiotrophin (Ptn) antagonizes Brd2 during neuronal differentiation by destabilizing Brd2's association with chromatin; Ptn-Brd2 interaction was identified by co-immunoprecipitation; Ptn knockdown reduces neuronal differentiation, while Ptn overexpression antagonizes Brd2 cell-cycle-stimulating activity. Co-immunoprecipitation, chromatin fractionation, Ptn knockdown/overexpression, neuronal differentiation assays, spinal cord and neural crest in vivo models Journal of cell science Medium 24695857
2020 RUNX2 and BRD2 co-immunoprecipitate and both occupy the RANKL promoter; mechanical strain reduces both RUNX2 and BRD2 occupancy at the RANKL promoter (ChIP) and decreases RANKL expression; strain also down-regulates BRD2 expression; RUNX2 knockdown prevents strain-induced RANKL down-regulation. Co-immunoprecipitation, ChIP at RANKL promoter, four-point bending strain assay, RUNX2 siRNA knockdown Gene: X Low 32550554
1998 p85/RING3 kinase is activated in multiple organs (lung, kidney, brain, liver, heart) after systemic administration of mitogens (EGF, PMA, IL-1β); anti-RING3 antibodies immunoprecipitate the mitogen-responsive p85 kinase activity from lung and brain, establishing that p85 and RING3 are the same enzyme. Autophosphorylation membrane assay, kinase immunoprecipitation from tissue lysates Oncogene Low 9528865

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses. Journal of immunology (Baltimore, Md. : 1950) 352 23420887
2008 The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription. Molecular cell 304 18406326
2015 BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells. Oncotarget 220 25989842
1999 Latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts with RING3, a homolog of the Drosophila female sterile homeotic (fsh) gene. Journal of virology 153 10559289
2009 Brd2 disruption in mice causes severe obesity without Type 2 diabetes. The Biochemical journal 144 19883376
2003 BRD2 (RING3) is a probable major susceptibility gene for common juvenile myoclonic epilepsy. American journal of human genetics 142 12830434
2000 RING3 kinase transactivates promoters of cell cycle regulatory genes through E2F. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 141 10965846
2009 Double bromodomain-containing gene Brd2 is essential for embryonic development in mouse. Developmental dynamics : an official publication of the American Association of Anatomists 130 19301389
2006 Kaposi's sarcoma-associated herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4- and BRD2/RING3-induced G1 cell cycle arrest. Journal of virology 129 16928766
2003 Markers of genetic susceptibility in human environmental hygiene and toxicology: the role of selected CYP, NAT and GST genes. International journal of hygiene and environmental health 121 12872524
2017 Distinct Roles of Brd2 and Brd4 in Potentiating the Transcriptional Program for Th17 Cell Differentiation. Molecular cell 119 28262505
2017 The BET Protein BRD2 Cooperates with CTCF to Enforce Transcriptional and Architectural Boundaries. Molecular cell 108 28388437
2004 Identification of unique, differentiation stage-specific patterns of expression of the bromodomain-containing genes Brd2, Brd3, Brd4, and Brdt in the mouse testis. Gene expression patterns : GEP 99 15261828
1997 Identification and characterization of BRDT: A testis-specific gene related to the bromodomain genes RING3 and Drosophila fsh. Genomics 99 9367677
2012 Genome-wide analysis of plant nat-siRNAs reveals insights into their distribution, biogenesis and function. Genome biology 98 22439910
2009 Genetic polymorphism in N-Acetyltransferase (NAT): Population distribution of NAT1 and NAT2 activity. Journal of toxicology and environmental health. Part B, Critical reviews 98 20183529
2005 Brd2/RING3 interacts with a chromatin-binding domain in the Kaposi's Sarcoma-associated herpesvirus latency-associated nuclear antigen 1 (LANA-1) that is required for multiple functions of LANA-1. Journal of virology 97 16227282
2006 Crystal structure of the human BRD2 bromodomain: insights into dimerization and recognition of acetylated histone H4. The Journal of biological chemistry 95 17148447
2010 Structural basis for acetylated histone H4 recognition by the human BRD2 bromodomain. The Journal of biological chemistry 94 20048151
2003 E mu-BRD2 transgenic mice develop B-cell lymphoma and leukemia. Blood 93 14563639
2018 HDAC11 suppresses the thermogenic program of adipose tissue via BRD2. JCI insight 90 30089714
2013 A structural basis for BRD2/4-mediated host chromatin interaction and oligomer assembly of Kaposi sarcoma-associated herpesvirus and murine gammaherpesvirus LANA proteins. PLoS pathogens 89 24146614
2008 The nucleobase-ascorbate transporter (NAT) family: genomics, evolution, structure-function relationships and physiological role. Molecular bioSystems 87 18414738
2012 A combination of H2A.Z and H4 acetylation recruits Brd2 to chromatin during transcriptional activation. PLoS genetics 86 23144632
2005 Bromodomain analysis of Brd2-dependent transcriptional activation of cyclin A. The Biochemical journal 85 15548137
2009 The chromatin-targeting protein Brd2 is required for neural tube closure and embryogenesis. Biochimica et biophysica acta 81 19362612
2004 A novel family of Ca2+/calmodulin-binding proteins involved in transcriptional regulation: interaction with fsh/Ring3 class transcription activators. Plant molecular biology 75 15316289
2004 Should HBV DNA NAT replace HBsAg and/or anti-HBc screening of blood donors? Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine 72 14980546
2016 BET Bromodomain Proteins Brd2, Brd3 and Brd4 Selectively Regulate Metabolic Pathways in the Pancreatic β-Cell. PloS one 69 27008626
1992 Cloned mouse N-acetyltransferases: enzymatic properties of expressed Nat-1 and Nat-2 gene products. Molecular pharmacology 62 1513324
2018 Transfusion-Transmitted Hepatitis E: NAT Screening of Blood Donations and Infectious Dose. Frontiers in medicine 61 29450199
2023 CRISPR Screen Reveals BRD2/4 Molecular Glue-like Degrader via Recruitment of DCAF16. ACS chemical biology 60 36656921
2022 BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2. Nature cell biology 60 35027731
2014 Targeting STAT5 in hematologic malignancies through inhibition of the bromodomain and extra-terminal (BET) bromodomain protein BRD2. Molecular cancer therapeutics 57 24435449
2020 LAMB3 promotes tumour progression through the AKT-FOXO3/4 axis and is transcriptionally regulated by the BRD2/acetylated ELK4 complex in colorectal cancer. Oncogene 56 32398865
2016 H2A.Z.1 Monoubiquitylation Antagonizes BRD2 to Maintain Poised Chromatin in ESCs. Cell reports 55 26804911
2013 The C-terminal domain of Brd2 is important for chromatin interaction and regulation of transcription and alternative splicing. Molecular biology of the cell 55 24048450
2022 BRD2 compartmentalizes the accessible genome. Nature genetics 51 35410381
2002 The pharmacogenetics of NAT: structural aspects. Pharmacogenomics 51 11966400
1997 Linkage of LMP, TAP, and RING3 with Mhc class I rather than class II genes in the zebrafish. Journal of immunology (Baltimore, Md. : 1950) 51 9550404
1988 Linkage of Nat and Es-1 in the mouse and development of strains congenic for N-acetyltransferase. The Journal of heredity 50 3209851
2018 Silencing of the lncRNA Zeb2-NAT facilitates reprogramming of aged fibroblasts and safeguards stem cell pluripotency. Nature communications 49 29311544
2001 Validation and standardisation of nucleic acid amplification technology (NAT) assays for the detection of viral contamination of blood and blood products. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 49 11163577
2000 Activation-induced nuclear translocation of RING3. Journal of cell science 49 10934046
2002 Latent nuclear antigen of Kaposi's sarcoma herpesvirus/human herpesvirus-8 induces and relocates RING3 to nuclear heterochromatin regions. The Journal of general virology 48 11752715
2006 Brd2 is a TBP-associated protein and recruits TBP into E2F-1 transcriptional complex in response to serum stimulation. Molecular and cellular biochemistry 47 17111193
2021 Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2/4-PFKP during tumorigenesis of advanced prostate cancer. Nucleic acids research 45 33849067
1999 Polymorphisms of the xenobiotic-metabolizing enzymes CYP1A1 and NAT-2 in systemic sclerosis and lupus erythematosus. Advances in experimental medicine and biology 45 10599336
2013 The double bromodomain protein Brd2 promotes B cell expansion and mitogenesis. Journal of leukocyte biology 42 24319289
2006 Association of BRD2 polymorphisms with photoparoxysmal response. Neuroscience letters 41 16516380
2019 Discovery of novel small molecule induced selective degradation of the bromodomain and extra-terminal (BET) bromodomain protein BRD4 and BRD2 with cellular potencies. Bioorganic & medicinal chemistry 37 31767403
2018 Histone H2A.Z Suppression of Interferon-Stimulated Transcription and Antiviral Immunity Is Modulated by GCN5 and BRD2. iScience 36 30240626
2012 Brd2 is required for cell cycle exit and neuronal differentiation through the E2F1 pathway in mouse neuroepithelial cells. Biochemical and biophysical research communications 36 22885183
2013 Rapid birth-and-death evolution of the xenobiotic metabolizing NAT gene family in vertebrates with evidence of adaptive selection. BMC evolutionary biology 35 23497148
2018 JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states. Epigenetics 33 30080437
2014 Pleiotrophin antagonizes Brd2 during neuronal differentiation. Journal of cell science 33 24695857
2013 Brd2 gene disruption causes "metabolically healthy" obesity: epigenetic and chromatin-based mechanisms that uncouple obesity from type 2 diabetes. Vitamins and hormones 33 23374712
2006 Bromodomain testis-specific protein is expressed in mouse oocyte and evolves faster than its ubiquitously expressed paralogs BRD2, -3, and -4. Genomics 33 17049203
2000 NAT and viral safety in blood transfusion. Vox sanguinis 32 10938964
1997 Chromosomal localization, gene structure and transcription pattern of the ORFX gene, a homologue of the MHC-linked RING3 gene. Gene 32 9373153
2013 Brd2 inhibits adipogenesis via the ERK1/2 signaling pathway in 3T3-L1 adipocytes. PloS one 31 24194944
2012 Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells. Journal of pineal research 31 22225631
1994 Expression of N-acetyltransferase (NAT) in cultured human uroepithelial cells. Carcinogenesis 30 8001235
2021 Targeting BET Proteins BRD2 and BRD3 in Combination with PI3K-AKT Inhibition as a Therapeutic Strategy for Ovarian Clear Cell Carcinoma. Molecular cancer therapeutics 29 33509905
2019 LYAR potentiates rRNA synthesis by recruiting BRD2/4 and the MYST-type acetyltransferase KAT7 to rDNA. Nucleic acids research 29 31504794
2017 Spatially restricted loading of BRD2 at DNA double-strand breaks protects H4 acetylation domains and promotes DNA repair. Scientific reports 29 29018219
2020 Integration of the Transcriptome and Genome-Wide Landscape of BRD2 and BRD4 Binding Motifs Identifies Key Superenhancer Genes and Reveals the Mechanism of Bet Inhibitor Action in Rheumatoid Arthritis Synovial Fibroblasts. Journal of immunology (Baltimore, Md. : 1950) 27 33288543
2018 DNA methylation of the BRD2 promoter is associated with juvenile myoclonic epilepsy in Caucasians. Epilepsia 27 29608786
2020 BRD2 induces drug resistance through activation of the RasGRP1/Ras/ERK signaling pathway in adult T-cell lymphoblastic lymphoma. Cancer communications (London, England) 25 32459053
2017 Brd4-Brd2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification. EMBO reports 25 28588073
2015 LRP1B, BRD2 and CACNA1D: new candidate genes in fetal metabolic programming of newborns exposed to maternal hyperglycemia. Epigenomics 25 26586120
2009 MnSOD genotype and prostate cancer risk as a function of NAT genotype and smoking status. In vivo (Athens, Greece) 25 19368118
2013 Identification of ta-siRNAs and cis-nat-siRNAs in cassava and their roles in response to cassava bacterial blight. Genomics, proteomics & bioinformatics 24 23665476
2022 BRD2 interconnects with BRD3 to facilitate Pol II transcription initiation and elongation to prime promoters for cell differentiation. Cellular and molecular life sciences : CMLS 23 35665862
2020 BRD2 regulation of sigma-2 receptor upon cholesterol deprivation. Life science alliance 23 33234676
2018 LTBSG1, a New Allele of BRD2, Regulates Panicle and Grain Development in Rice by Brassinosteroid Biosynthetic Pathway. Genes 23 29891831
2011 The bromodomain-containing gene BRD2 is regulated at transcription, splicing, and translation levels. Journal of cellular biochemistry 23 21608014
2001 Short tandem repeat (STR) haplotypes in HLA: an integrated 50-kb STR/linkage disequilibrium/gene map between the RING3 and HLA-B genes and identification of STR haplotype diversification in the class III region. European journal of human genetics : EJHG 23 11528504
2022 Natural variation of the BRD2 allele affects plant height and grain size in rice. Planta 22 35780402
2021 Dissecting the Role of BET Bromodomain Proteins BRD2 and BRD4 in Human NK Cell Function. Frontiers in immunology 22 33717143
2023 Cellular effects of NAT-mediated histone N-terminal acetylation. Journal of cell science 21 37013828
2019 Small Molecule and Pooled CRISPR Screens Investigating IL17 Signaling Identify BRD2 as a Novel Contributor to Keratinocyte Inflammatory Responses. ACS chemical biology 21 30938974
2006 N-acetyltransferase (Nat) 1 and 2 expression in Nat2 knockout mice. The Journal of pharmacology and experimental therapeutics 20 16857729
2004 Bromodomain containing 2 (Brd2) is expressed in distinct patterns during ovarian folliculogenesis independent of FSH or GDF9 action. Molecular reproduction and development 20 15112318
2020 Mechanical strain-mediated reduction in RANKL expression is associated with RUNX2 and BRD2. Gene: X 19 32550554
2018 Evolution of substrate specificity in the Nucleobase-Ascorbate Transporter (NAT) protein family. Microbial cell (Graz, Austria) 19 29850465
1998 Stimulation of p85/RING3 kinase in multiple organs after systemic administration of mitogens into mice. Oncogene 19 9528865
2024 Phosphocreatine Promotes Epigenetic Reprogramming to Facilitate Glioblastoma Growth Through Stabilizing BRD2. Cancer discovery 18 38563585
2020 Brd2/4 and Myc regulate alternative cell lineage programmes during early osteoclast differentiation in vitro. iScience 18 33490899
2018 Occult HBV infection in HIV-infected adults and evaluation of pooled NAT for HBV. Journal of viral hepatitis 18 29316078
2014 Sex-specific behavioral traits in the Brd2 mouse model of juvenile myoclonic epilepsy. Genes, brain, and behavior 18 25130458
2006 BRD2 is one of BRD7-interacting proteins and its over-expression could initiate apoptosis. Molecular and cellular biochemistry 18 16786191
1998 Nucleotide sequence of the ring3 gene in the class II region of the mouse MHC and its abundant expression in testicular germ cells. Genomics 18 9693039
2022 Epigenetic regulation of EIF4A1 through DNA methylation and an oncogenic role of eIF4A1 through BRD2 signaling in prostate cancer. Oncogene 17 35361883
2004 NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant. BMC medical genetics 17 15142281
2017 AA-NAT, MT1 and MT2 Correlates with Cancer Stem-Like Cell Markers in Colorectal Cancer: Study of the Influence of Stage and p53 Status of Tumors. International journal of molecular sciences 15 28604612
2009 Two HBV DNA+/HBsAg- blood donors identified by HBV NAT in Shenzhen, China. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 15 19487161
2018 NF-κB signaling activation via increases in BRD2 and BRD4 confers resistance to the bromodomain inhibitor I-BET151 in U937 cells. Leukemia research 14 30300821
2015 The Epigenetic Reader BRD2 as a Specific Modulator of PAI-1 Expression in Lipopolysaccharide-Stimulated Mouse Primary Astrocytes. Neurochemical research 14 26349765
2021 O-alkyl and o-benzyl hesperetin derivative-1L attenuates inflammation and protects against alcoholic liver injury via inhibition of BRD2-NF-κB signaling pathway. Toxicology 13 34974135

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