Affinage

BRD2

Bromodomain-containing protein 2 · UniProt P25440

Length
801 aa
Mass
88.1 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BRD2 is a BET family double-bromodomain protein that functions as an epigenetic reader of histone acetylation marks—principally H4K12ac and H4K5acK8ac—and serves as a transcriptional co-regulator and chromatin organizer across diverse cellular processes including cell cycle progression, inflammatory gene expression, and metabolic regulation. Its first bromodomain (BD1) forms a homodimer that specifically recognizes H4K12ac, and BRD2 is recruited to chromatin through combinatorial recognition of hyperacetylated H4 on H2A.Z-containing nucleosomes; once bound, it scaffolds transcription factor complexes (E2F-1/2, STAT3, STAT5, SREBP2, TBP) and chromatin remodelers (SWI/SNF), facilitates TAF3-dependent RNA Pol II initiation, and suppresses R-loop formation during elongation (PMID:17148447, PMID:18406326, PMID:35665862, PMID:15548137, PMID:28262505). BRD2 co-localizes genome-wide with CTCF and cohesin to maintain topological domain boundaries, and upon cohesin loss it drives A-compartment chromatin mixing through its double bromodomain and low-complexity domain (PMID:28388437, PMID:35410381). BRD2 protein stability is regulated by phosphocreatine, which competes with the E3 ligase SPOP for BRD2 binding to prevent its poly-ubiquitination and proteasomal degradation (PMID:38563585).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 Medium

    Establishing BRD2 as a mitogen-activated signaling kinase addressed whether this bromodomain protein had catalytic activity beyond chromatin reading.

    Evidence Autophosphorylation assay and immunoprecipitation after systemic EGF/PMA/IL-1β administration in mice

    PMID:9528865

    Open questions at the time
    • Kinase substrate specificity unknown
    • Later studies questioned whether BRD2 itself is the kinase or recruits one (PMID:10559289)
    • No structural basis for kinase activity identified
  2. 2000 High

    Linking BRD2 to E2F-dependent cell cycle gene transactivation established its core function as a transcriptional co-regulator of proliferation.

    Evidence Reporter assays with kinase-dead mutant, co-purification of E2F-1/E2F-2, NLS mutagenesis and nuclear translocation studies

    PMID:10934046 PMID:10965846

    Open questions at the time
    • Whether BRD2 possesses intrinsic kinase activity remained debated
    • Mechanism of E2F recruitment to specific promoters not yet defined
  3. 2005 High

    Demonstrating that BRD2 recruits E2F and histone acetyltransferase activity to the cyclin A promoter in S-phase resolved how BRD2 activates a specific cell cycle target.

    Evidence Co-IP, ChIP at cyclin A promoter, cell cycle analysis upon BRD2 overexpression

    PMID:15548137

    Open questions at the time
    • Identity of the H4 acetyltransferase in the BRD2 complex not determined
    • Genome-wide target repertoire unknown
  4. 2006 High

    Structural determination of BRD2-BD1 bound to H4K12ac defined the molecular basis of acetyl-lysine recognition and revealed an unexpected homodimeric architecture.

    Evidence X-ray crystallography of BD1 alone and with H4K12ac peptides, solution biochemistry

    PMID:17148447 PMID:20048151

    Open questions at the time
    • BD2 structure and its distinct substrate specificity not yet resolved
    • Functional significance of dimerization in vivo not tested
  5. 2006 Medium

    Proteomic identification of SWI/SNF subunits, co-activators, co-repressors, TBP, and BRD7 in BRD2 complexes expanded BRD2's role from a single-TF adapter to a multi-complex scaffold.

    Evidence Affinity purification–mass spectrometry, co-IP, yeast two-hybrid (BRD7), domain mapping (TBP interaction)

    PMID:16512664 PMID:16786191 PMID:17111193

    Open questions at the time
    • Stoichiometry and exclusivity of distinct BRD2 complexes unknown
    • BRD7 interaction from yeast two-hybrid not independently confirmed by reciprocal co-IP
    • Functional consequence of SWI/SNF recruitment not directly tested
  6. 2008 High

    Reconstituting BRD2-dependent transcription through nucleosomes in vitro proved it functions as a histone chaperone that enables Pol II elongation on acetylated chromatin.

    Evidence Defined in vitro transcription system with nucleosomal templates, ChIP for BRD2 along transcribed genes

    PMID:18406326

    Open questions at the time
    • Whether histone chaperone activity is separable from bromodomain-acetylation reading not resolved
    • Contribution relative to other elongation factors unknown
  7. 2012 High

    Showing that BRD2 recruitment requires both H4 hyperacetylation and H2A.Z nucleosome features revealed a combinatorial chromatin-reading mechanism beyond simple acetyl-lysine binding.

    Evidence Nucleosome purification/MS, ChIP at AR-regulated genes, pharmacologic inhibition

    PMID:23144632 PMID:26804911

    Open questions at the time
    • Direct structural interface between BRD2 and H2A.Z not mapped
    • How H2A.Z monoubiquitylation mechanistically blocks BRD2 binding unclear
  8. 2013 High

    Genome-wide transcriptomic and ChIP studies established BRD2 as a regulator of >1400 genes and ~290 alternative splicing events, and as a critical reader at inflammatory cytokine promoters.

    Evidence BRD2 knockdown + RNA-seq, ChIP at IL-6/TNF-α promoters, brd2-lo genetic mouse model with LPS challenge, live-cell FRAP

    PMID:23420887 PMID:24048450

    Open questions at the time
    • Mechanism of alternative splicing regulation by BRD2 unknown
    • Whether BRD2 directly recruits splicing factors not tested
  9. 2017 High

    Genome-wide co-localization of BRD2 with CTCF and the discovery that BRD2 depletion weakens topological domain boundaries established BRD2 as a chromatin architectural factor, not merely a transcriptional co-activator.

    Evidence ChIP-seq, Hi-C, single-molecule mRNA FISH upon BRD2 depletion and site-specific CTCF disruption; co-IP of BRD2–CTCF–cohesin in Th17 cells

    PMID:28262505 PMID:28388437

    Open questions at the time
    • Whether BRD2 directly contacts CTCF or is bridged by cohesin not resolved
    • Domain of BRD2 mediating CTCF interaction not mapped
  10. 2022 High

    Acute depletion studies revealed that BRD2 drives A-compartment chromatin mixing upon cohesin loss, is antagonized by BRD4, facilitates TAF3-dependent Pol II initiation at low-H3K4me3 promoters, and suppresses R-loops during elongation—clarifying its dual architectural and transcriptional functions.

    Evidence Auxin-inducible degron, Hi-C, ChIP-seq, DRIP-seq, quantitative proteomics

    PMID:35410381 PMID:35665862

    Open questions at the time
    • Whether R-loop suppression is direct or via recruited helicases unknown
    • Structural basis for BRD2–TAF3 cooperation not determined
  11. 2022 High

    CRISPRi screening identified BRD2 as the essential transcriptional activator of ACE2 in lung epithelia, linking its chromatin-reading function to SARS-CoV-2 entry and interferon-stimulated gene control.

    Evidence CRISPRi screen, BRD2-specific inhibitor ABBV-744, in vivo hamster infection model

    PMID:35027731

    Open questions at the time
    • Whether BRD2 acts at ACE2 through CTCF boundary effects or direct promoter activation not distinguished
    • Therapeutic window of BRD2 inhibition for antiviral use undefined
  12. 2024 High

    Discovery that phosphocreatine stabilizes BRD2 by competing with the E3 ligase SPOP for binding revealed a metabolite-controlled protein stability mechanism governing BRD2 levels and downstream cell proliferation.

    Evidence Co-IP (SPOP–BRD2), ubiquitination assays, pharmacologic disruption of PCr biosynthesis, mouse GBM models

    PMID:38563585

    Open questions at the time
    • Structural basis of PCr–BRD2 interaction not resolved
    • Whether SPOP–BRD2 regulation operates in non-cancer contexts unknown
    • Relative contribution of SPOP vs. DCAF16-mediated degradation (PMID:36656921) in physiological turnover unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of full-length BRD2 on nucleosomes, whether BRD2 possesses intrinsic kinase activity, the mechanism by which it regulates alternative splicing, and how its architectural and transcriptional functions are coordinately regulated.
  • No full-length BRD2–nucleosome structure
  • Intrinsic kinase activity never reconstituted with purified protein
  • Alternative splicing mechanism completely uncharacterized
  • Relative physiological importance of BRD2 vs. BRD3/BRD4 at shared vs. unique target sites unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0042393 histone binding 6 GO:0060090 molecular adaptor activity 5 GO:0044183 protein folding chaperone 1
Localization
GO:0005694 chromosome 4 GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3
Pathway
R-HSA-74160 Gene expression (Transcription) 11 R-HSA-4839726 Chromatin organization 6 R-HSA-1640170 Cell Cycle 5 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 2
Partners
CTCFE2F1E2F2SPOPSREBP2STAT3TAF3TBP
Complex memberships
BET-CTCF-cohesinSWI/SNF

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 BRD2 (and BRD3) associate preferentially with hyperacetylated chromatin along entire lengths of transcribed genes, enriched at H4K5ac, H4K12ac, and H3K14ac marks; BRD2 enables RNA polymerase II to transcribe through nucleosomes in a defined in vitro transcription system dependent on specific H4 modifications, and BRD2 has intrinsic histone chaperone activity. In vitro transcription assay through nucleosomes, ChIP, histone modification analysis Molecular cell High 18406326
2006 Crystal structure of the BRD2 N-terminal bromodomain (BD1) reveals a homodimer with two acetyllysine-binding pockets; BRD2 BD1 specifically recognizes histone H4 tail acetylated at Lys12 (H4K12ac), and biochemical studies confirmed BD1 dimer formation in solution. X-ray crystallography, biochemical binding studies The Journal of biological chemistry High 17148447
2010 Crystal structures of BRD2-BD1 in complex with three different H4K12ac peptides show that BD1 recognizes H4K12ac, with hypoacetylated Lys8 binding at the dimer interface cavity; mutation of Lys8 in the H4K12ac tail decreased binding, implicating Lys8 in recognition. X-ray crystallography, mutational binding studies The Journal of biological chemistry High 20048151
2000 RING3/BRD2 is a nuclear-localized serine-threonine kinase that transactivates E2F-dependent cell cycle gene promoters (cyclin D1, cyclin A, cyclin E, DHFR) in a Ras-signaling-dependent manner; kinase-deficient point mutant fails to transactivate; anti-RING3 affinity chromatography copurifies E2F-1 and E2F-2. Transient transfection/reporter assay, site-directed mutagenesis, immunoaffinity chromatography/co-purification Cell growth & differentiation High 10965846
2000 RING3/BRD2 is constitutively nuclear in cycling cells but delocalized in serum-starved fibroblasts; serum stimulation triggers nuclear translocation dependent on a monopartite nuclear localization sequence; nuclear RING3 forms complexes with E2F proteins and transactivates E2F-regulated cell cycle promoters. Immunostaining, confocal microscopy, site-directed mutagenesis of NLS, co-immunoprecipitation, reporter assays Journal of cell science High 10934046
2006 Affinity purification of BRD2 from cultured cells followed by mass spectrometry identifies a multicomponent nuclear complex containing co-activators, co-repressors, and Swi/Snf chromatin remodeling complex subunits. Affinity purification, mass spectrometry/proteomics, immunoblot confirmation Journal of proteome research Medium 16512664
2005 BRD2 mediates recruitment of both E2F transcription factors and histone H4-directed acetyltransferase activity to the cyclin A promoter; in S-phase, BRD2-containing complexes contain E2F-1, E2F-2, and histone H4 acetyltransferase activity; overexpression of BRD2 accelerates the cell cycle through increased cyclin A expression. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), overexpression/cell cycle analysis The Biochemical journal High 15548137
2006 BRD2 (RING3) is recruited to nuclear heterochromatin regions by KSHV LANA, which induces RING3 gene expression; RING3 and LANA co-localize in nuclear bodies and RING3 remains chromosome-associated during mitosis in KSHV-infected cells; BRD2/RING3 delays S-phase entry when overexpressed, and KSHV LANA-1 partly releases cells from BRD2-induced G1 arrest. Immunofluorescence/subcellular localization, transfection, cell cycle analysis, reporter assays Journal of virology Medium 16928766
1999 KSHV LANA interacts with RING3/BRD2 via the ET domain of RING3; this interaction results in phosphorylation of serine and threonine residues in the C-terminal region of LANA; RING3 itself is not a kinase but recruits an unidentified serine/threonine kinase into the complex. Co-immunoprecipitation, in vitro binding, phosphorylation assay Journal of virology Medium 10559289
2006 BRD2 is a TBP-associated protein; a 26-amino-acid peptide in the first bromodomain of BRD2 is essential for BRD2-TBP interaction; serum stimulation induces formation of a BRD2-E2F-1-TBP complex in vivo; BRD2 recruits TBP into the E2F-1 transcriptional complex and this is required for BRD2-dependent transactivation of E2F-1-responsive promoters. Co-immunoprecipitation, domain mapping with peptide, reporter assays Molecular and cellular biochemistry Medium 17111193
2012 BRD2 is recruited to chromatin through a combination of hyperacetylated H4 on H2A.Z-containing nucleosomes and additional features on H2A.Z itself; BRD2 is recruited to AR-regulated genes in an H2A.Z-dependent manner, and chemical inhibition of BRD2 recruitment greatly inhibits AR-regulated gene expression. Nucleosome purification/mass spectrometry, co-immunoprecipitation, ChIP, pharmacologic inhibition with expression readout PLoS genetics High 23144632
2013 The C-terminal domain of BRD2 is critical for chromatin association (beyond histone acetylation recognition); BRD2 regulates both transcription and alternative splicing of ~1450 and ~290 target genes respectively; live-cell imaging quantified the average binding time of BRD2 to chromatin and the contributions of individual domains. Genome-wide screen (knockdown + transcriptomics), co-immunoprecipitation, live-cell FRAP/imaging, domain deletion analysis Molecular biology of the cell High 24048450
2013 BRD2 and BRD4 physically associate with the promoters of inflammatory cytokine genes (IL-6, TNF-α) in macrophages as shown by ChIP; Brd2 genetic disruption and siRNA knockdown impair proinflammatory cytokine production, establishing BRD2 as an essential reader of histone acetylation marks at inflammatory gene promoters. ChIP, siRNA knockdown, genetic hypomorph model (brd2 lo mice), in vivo LPS model Journal of immunology High 23420887
2017 During Th17 cell differentiation, BRD2 associates with the chromatin insulator CTCF and the cohesin complex to support cis-regulatory enhancer assembly; BRD2 binds transcription factor STAT3 in an acetylation-sensitive manner and facilitates STAT3 recruitment to active enhancers occupied by IRF4 and BATF. ChIP-seq, Co-IP, quantitative proteomics, CRISPR/knockdown Molecular cell High 28262505
2017 BRD2, but not BRD4, co-localizes genome-wide with the architectural protein CTCF; CTCF recruits BRD2 to co-bound sites while BRD2 is dispensable for CTCF occupancy; BRD2 depletion weakens topological domain boundaries co-occupied by CTCF/BRD2, enabling regulatory influence to spread between adjacent genes. ChIP-seq, HiC, single-molecule mRNA FISH, BRD2 depletion, site-specific CTCF disruption Molecular cell High 28388437
2022 BRD2 promotes spatial mixing and compartmentalization of active (A-compartment) chromatin after cohesin loss; this activity requires BRD2's double bromodomain to recognize acetylated targets and its low-complexity domain for binding partners; genome compartmentalization by BRD2 is antagonized by cohesin and by BRD4, both of which inhibit BRD2 chromatin binding. Hi-C, ChIP-seq, acute protein degradation (auxin-inducible degron), polymer simulation Nature genetics High 35410381
2018 HDAC11 suppresses the brown adipose tissue thermogenic program through physical association with BRD2; HDAC11 catalytic activity is required for this repression and the mechanism depends on direct protein-protein interaction with BRD2. Co-immunoprecipitation, HDAC11 knockout mice, cell-based thermogenic gene expression assays, catalytic mutant JCI insight Medium 30089714
2014 Among BET family members, BRD2 is identified as the critical mediator of STAT5-dependent transcription; BRD2 knockdown specifically reduces STAT5-dependent (but not STAT3-dependent) target gene expression in leukemia and lymphoma cells. siRNA knockdown of individual BET members, reporter assays, endogenous target gene expression analysis Molecular cancer therapeutics Medium 24435449
2022 BRD2 is required for ACE2 transcription in human lung epithelial cells and cardiomyocytes; BRD2 inhibition blocks endogenous ACE2 expression and SARS-CoV-2 infection; BRD2 also controls transcription of interferon-stimulated genes in response to SARS-CoV-2 infection. CRISPRi screen, BRD2 inhibitors (ABBV-744), in vivo hamster model, qPCR/ChIP Nature cell biology High 35027731
2022 BRD2 is required for TAF3-mediated RNA Pol II initiation at promoters with low H3K4me3 levels; BRD2 suppresses R-loop formation during Pol II elongation; BRD2 and BRD3 function additively, independently, or antagonistically at different promoters. Acute protein degradation (BRD2/BRD3 depletion), ChIP-seq, R-loop detection (DRIP-seq), quantitative proteomics Cellular and molecular life sciences High 35665862
2020 BRD2 co-occupies the RANKL promoter with RUNX2; BRD2 and RUNX2 co-immunoprecipitate and BRD2 occupies the RUNX2 promoter; mechanical strain reduces BRD2 expression and BRD2 occupancy at the RANKL promoter, contributing to strain-mediated RANKL down-regulation. ChIP, co-immunoprecipitation, siRNA knockdown, mechanical strain model Gene: X Medium 32550554
2019 BRD2 (not BRD3 or BRD4) is identified as the critical mediator of IL-17A/TNF-induced IL-8 and inflammatory chemokine production in keratinocytes; BRD2 knockout reduces expression of 438 IL-17A/TNF-dependent genes. CRISPR screen, siRNA knockdown, RNA-seq, 3D organotypic cultures ACS chemical biology High 30938974
2018 BRD2 co-localizes with H4K5acK8ac at active enhancers and promoters; BRD2 shows stronger association with H4K5acK8ac than H3K27ac; JQ1-mediated BET inhibition completely removes BRD2 from chromatin without globally altering H4 hyperacetylation levels, indicating that BRD2 binding is driven by H4 hyperacetylation rather than vice versa. ChIP-seq (BRD2, H4K5acK8ac, H3K27ac), JQ1 treatment, RNA-seq Epigenetics Medium 30080437
2016 H2A.Z.1 monoubiquitylation antagonizes BRD2 recruitment at bivalent gene promoters in embryonic stem cells; loss of ubiquitylation leads to BRD2 gain at de-repressed promoters, and BRD2 inhibition restores gene silencing, defining an antagonistic relationship between H2A.Z.1ub and BRD2. Quantitative proteomics, ChIP-seq, BRD2 inhibition, H2A.Z.1 K→R mutation Cell reports High 26804911
2020 BRD2 promotes drug resistance in T-cell lymphoblastic lymphoma through transcriptional activation of RasGRP1 via E2F1/BRD2 co-occupancy of the RasGRP1 promoter, leading to Ras/ERK pathway activation. ChIP assay (E2F1/BRD2 at RasGRP1 promoter), Ras pull-down assay, siRNA knockdown, in vitro/in vivo drug resistance models Cancer communications Medium 32459053
2019 LYAR recruits BRD2 to the rDNA promoter and transcribed regions via upstream binding factor; BRD2 is required for recruitment of the MYST acetyltransferase KAT7 to rDNA, leading to enhanced local H4 acetylation and increased rRNA synthesis; BRD2 also facilitates BRD4 recruitment to rDNA. Co-immunoprecipitation, ChIP, knockdown experiments Nucleic acids research Medium 31504794
2020 BRD2 cooperates with acetylated ELK4 (acetylated at K125) to regulate LAMB3 transcription in colorectal cancer by directly binding the LAMB3 promoter; acetylation of ELK4 at K125 enhances ELK4-BRD2 interaction; JQ1 disrupts ELK4-BRD2 interaction and reduces BRD2 promoter binding. ChIP, co-immunoprecipitation, acetylation site mutagenesis, BET inhibitor treatment Oncogene Medium 32398865
2018 BRD2 (and GCN5) are required for IFN-stimulated removal of H2A.Z from ISG promoters; interference with BRD2 impairs IFN-driven H2A.Z eviction, ISGF3 recruitment, ISG mRNA expression, and antiviral immunity. siRNA knockdown, ChIP, IFN stimulation assays, antiviral protection assays iScience Medium 30240626
2020 BRD2 silencing (but not BRD3 or BRD4) prevents sigma-2 receptor (S2R) upregulation upon cholesterol deprivation; 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. siRNA knockdown, co-immunoprecipitation, ChIP-qPCR Life science alliance Medium 33234676
2024 Phosphocreatine (PCr) inhibits poly-ubiquitination of BRD2 by competing with E3 ubiquitin ligase SPOP for BRD2 binding, thereby stabilizing BRD2 protein; disruption of PCr biosynthesis leads to BRD2 degradation, reduction of its transcriptional targets, and inhibition of chromosome segregation and cell proliferation. Co-immunoprecipitation (SPOP-BRD2), ubiquitination assays, pharmacologic PCr biosynthesis disruption, mouse GBM models Cancer discovery High 38563585
2006 BRD2 (BRD7-interacting protein) identified by yeast two-hybrid; co-immunoprecipitation confirms BRD2-BRD7 interaction in mammalian cells; the region from amino acids 430–798 of BRD2 is critical for BRD7 interaction; BRD2 localizes to the nucleus with diffuse or dotted patterns, and over-expression initiates apoptosis. Yeast two-hybrid, co-immunoprecipitation, GFP localization, domain deletion Molecular and cellular biochemistry Low 16786191
2017 In pluripotent stem cells, BRD4 downregulation facilitates pluripotent exit and drives enhanced BRD2 occupancy at Nodal gene regulatory elements (NREs), unveiling a specific function for BRD2 in Nodal-Smad2 differentiative signaling; BRD4-BRD2 isoform switching at NREs coordinates pluripotent exit with lineage specification. Small molecule screen, ChIP, BRD4 knockdown, Smad2 reporter assays EMBO reports Medium 28588073
2013 BRD2 binds the cyclin A promoter in B cells (ChIP), increases cyclin A mRNA and protein levels, and promotes S-phase progression in mitogen-stimulated primary B cells; forced BRD2 expression in hematopoietic stem cells expands the B-cell compartment and increases mature B-cell mitogenic responsiveness. ChIP, lentiviral forced expression, hematopoietic stem cell reconstitution, flow cytometry, cell cycle analysis Journal of leukocyte biology Medium 24319289
2014 Pleiotrophin (PTN) antagonizes BRD2 cell-cycle-stimulating activity during neuronal differentiation by destabilizing BRD2 association with chromatin; PTN knockdown reduces neuronal differentiation, and PTN-BRD2 interaction was identified as controlling the balance between proliferation and differentiation in the vertebrate nervous system. Co-immunoprecipitation, chromatin binding assays, PTN knockdown, neuronal differentiation assays Journal of cell science Medium 24695857
2013 NMR spectroscopy identified a specific binding site for the ET domains of BRD2/4 on KSHV kLANA C-terminal domain; functional studies with multiple kLANA mutants established that the ET binding site is required for nuclear speckle formation and latent viral replication. NMR spectroscopy, X-ray crystallography of LANA CTD, mutagenesis, functional latency assays PLoS pathogens High 24146614
2023 A JQ1-based monovalent compound acts as a molecular glue degrader by driving the interaction between DCAF16 (a Cul4 E3 ligase component) and BRD2/4, promoting their ubiquitin-proteasome-dependent degradation; CRISPR screen identified DCAF16 as essential for compound activity. CRISPR/Cas9 knockout screen, co-immunoprecipitation, degradation assays ACS chemical biology High 36656921
2016 siRNA-specific inhibition of both Brd2 and Brd4 (but not one alone) enhances insulin transcription in pancreatic β-cells, increasing insulin content; inhibition of Brd2 alone increases fatty acid oxidation, demonstrating distinct metabolic roles for individual BET proteins. BET-specific siRNA knockdown, insulin secretion/content assays, fatty acid oxidation assays PloS one Medium 27008626
2013 Brd2 knockdown in obese mice prevents obesity-induced inflammatory responses and protects from insulin resistance, glucose intolerance, and pancreatic β-cell dysfunction, uncoupling obesity from type 2 diabetes. In vivo siRNA/genetic knockdown in mouse obesity model, metabolic assays Vitamins and hormones Medium 23374712
1998 p85/RING3 kinase (BRD2) is activated in multiple organs (lung, kidney, brain, liver, heart) following systemic administration of EGF, PMA, or IL-1β in mice; anti-RING3 antibodies immunoprecipitated the PMA-responsive p85 activity, confirming identity. Autophosphorylation membrane kinase assay, immunoprecipitation, in vivo mitogen administration Oncogene Medium 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) 346 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 218 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
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 140 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 128 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 127 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
2006 Identification of transcription complexes that contain the double bromodomain protein Brd2 and chromatin remodeling machines. Journal of proteome research 119 16512664
2017 Distinct Roles of Brd2 and Brd4 in Potentiating the Transcriptional Program for Th17 Cell Differentiation. Molecular cell 118 28262505
2001 The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis Cleaves and inactivates plasminogen activator inhibitor type 1. The Journal of biological chemistry 108 11325965
2017 The BET Protein BRD2 Cooperates with CTCF to Enforce Transcriptional and Architectural Boundaries. Molecular cell 107 28388437
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
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 97 15261828
2012 Genome-wide analysis of plant nat-siRNAs reveals insights into their distribution, biogenesis and function. Genome biology 96 22439910
2006 Epidemiology of HBV infection in Asian blood donors: emphasis on occult HBV infection and the role of NAT. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 95 16831692
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 88 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 88 24146614
2012 A combination of H2A.Z and H4 acetylation recruits Brd2 to chromatin during transcriptional activation. PLoS genetics 86 23144632
2008 The nucleobase-ascorbate transporter (NAT) family: genomics, evolution, structure-function relationships and physiological role. Molecular bioSystems 86 18414738
2005 Bromodomain analysis of Brd2-dependent transcriptional activation of cyclin A. The Biochemical journal 84 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
1997 Cytosolic arylamine N-acetyltransferase (NAT) deficiency in the dog and other canids due to an absence of NAT genes. Biochemical pharmacology 74 9296352
2016 BET Bromodomain Proteins Brd2, Brd3 and Brd4 Selectively Regulate Metabolic Pathways in the Pancreatic β-Cell. PloS one 67 27008626
2011 GABAergic neuron deficit as an idiopathic generalized epilepsy mechanism: the role of BRD2 haploinsufficiency in juvenile myoclonic epilepsy. PloS one 60 21887291
2018 Transfusion-Transmitted Hepatitis E: NAT Screening of Blood Donations and Infectious Dose. Frontiers in medicine 59 29450199
2023 CRISPR Screen Reveals BRD2/4 Molecular Glue-like Degrader via Recruitment of DCAF16. ACS chemical biology 58 36656921
2022 BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2. Nature cell biology 58 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 54 24048450
1999 Rapid detection of CYP1A1, CYP2D6, and NAT variants by multiplex polymerase chain reaction and allele-specific oligonucleotide assay. Analytical biochemistry 54 10542112
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
2022 BRD2 compartmentalizes the accessible genome. Nature genetics 50 35410381
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
2007 A multicenter study of BRD2 as a risk factor for juvenile myoclonic epilepsy. Epilepsia 46 17437413
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
2021 Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2/4-PFKP during tumorigenesis of advanced prostate cancer. Nucleic acids research 44 33849067
2013 The double bromodomain protein Brd2 promotes B cell expansion and mitogenesis. Journal of leukocyte biology 42 24319289
2012 Identification of the substrate recognition and transport pathway in a eukaryotic member of the nucleobase-ascorbate transporter (NAT) family. PloS one 41 22848666
2006 Association of BRD2 polymorphisms with photoparoxysmal response. Neuroscience letters 41 16516380
1999 Age-related differences in serum melatonin and pineal NAT activity and in the response of rat pineal to a 50-Hz magnetic field. Life sciences 41 10374919
2021 Bromodomain-containing proteins BRD1, BRD2, and BRD13 are core subunits of SWI/SNF complexes and vital for their genomic targeting in Arabidopsis. Molecular plant 40 33771698
2015 The Legacy of Nat Sternberg: The Genesis of Cre-lox Technology. Annual review of virology 39 26958905
2018 Histone H2A.Z Suppression of Interferon-Stimulated Transcription and Antiviral Immunity Is Modulated by GCN5 and BRD2. iScience 36 30240626
2013 Rapid birth-and-death evolution of the xenobiotic metabolizing NAT gene family in vertebrates with evidence of adaptive selection. BMC evolutionary biology 34 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
2008 The effect of temperature on Natural Antisense Transcript (NAT) expression in Aspergillus flavus. Current genetics 32 18813928
2000 NAT and viral safety in blood transfusion. Vox sanguinis 32 10938964
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
2003 Cytochrome P450 (CYP) 1A2, sulfotransferase (SULT) 1A1, and N-acetyltransferase (NAT) 2 polymorphisms and susceptibility to urothelial cancer. Journal of cancer research and clinical oncology 30 14648207
2000 Effects of handling and storage of blood on the stability of hepatitis C virus RNA: implications for NAT testing in transfusion practice. Vox sanguinis 30 10838513
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
2018 DNA methylation of the BRD2 promoter is associated with juvenile myoclonic epilepsy in Caucasians. Epilepsia 27 29608786
2018 Hepatitis E virus blood donor NAT screening: as much as possible or as much as needed? Transfusion 27 30548866
2009 Nutritional AMD treatment phase I (NAT-1): feasibility of oral DHA supplementation in age-related macular degeneration. European journal of ophthalmology 27 19123156
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
2021 Bromodomain-containing subunits BRD1, BRD2, and BRD13 are required for proper functioning of SWI/SNF complexes in Arabidopsis. Plant communications 24 34327319
2017 Synthetic nat- or ent-steroids in as few as five chemical steps from epichlorohydrin. Nature chemistry 24 29256503
2008 Standardization of nucleic acid amplification technique (NAT)-based assays for different genotypes of parvovirus B19: a meeting summary. Vox sanguinis 24 18171331
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
2013 Identification of ta-siRNAs and cis-nat-siRNAs in cassava and their roles in response to cassava bacterial blight. Genomics, proteomics & bioinformatics 23 23665476
2011 The bromodomain-containing gene BRD2 is regulated at transcription, splicing, and translation levels. Journal of cellular biochemistry 23 21608014
2023 Cellular effects of NAT-mediated histone N-terminal acetylation. Journal of cell science 21 37013828
2021 Dissecting the Role of BET Bromodomain Proteins BRD2 and BRD4 in Human NK Cell Function. Frontiers in immunology 21 33717143
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
2022 Natural variation of the BRD2 allele affects plant height and grain size in rice. Planta 19 35780402
1998 Stimulation of p85/RING3 kinase in multiple organs after systemic administration of mitogens into mice. Oncogene 19 9528865
2020 Mechanical strain-mediated reduction in RANKL expression is associated with RUNX2 and BRD2. Gene: X 18 32550554
2020 Brd2/4 and Myc regulate alternative cell lineage programmes during early osteoclast differentiation in vitro. iScience 18 33490899
2018 Evolution of substrate specificity in the Nucleobase-Ascorbate Transporter (NAT) protein family. Microbial cell (Graz, Austria) 18 29850465
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
2024 Phosphocreatine Promotes Epigenetic Reprogramming to Facilitate Glioblastoma Growth Through Stabilizing BRD2. Cancer discovery 17 38563585
2018 Occult HBV infection in HIV-infected adults and evaluation of pooled NAT for HBV. Journal of viral hepatitis 17 29316078
2004 NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant. BMC medical genetics 17 15142281