{"gene":"BRD1","run_date":"2026-06-09T22:02:45","timeline":{"discoveries":[{"year":2011,"finding":"BRD1 (BRPF2) forms a novel histone acetyltransferase complex with HBO1 and bridges HBO1 to its activator ING4; this Hbo1-Brd1 complex is responsible for global acetylation of histone H3 at lysine 14 (H3K14ac) in erythroblasts, and Brd1-deficient embryos show profoundly decreased H3K14 acetylation and impaired fetal liver erythropoiesis.","method":"Biochemical co-immunoprecipitation, genome-wide ChIP mapping in erythroblasts, conditional knockout mouse model with phenotypic rescue by Gata1 forced expression","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, genome-wide ChIP, KO mouse with specific phenotypic readout and partial rescue experiment across multiple orthogonal methods in one study","pmids":["21753189"],"is_preprint":false},{"year":2014,"finding":"Brd1 localizes at Cd8 gene enhancers in thymocytes as part of the Hbo1 HAT complex and is required for H3K14 acetylation at these enhancers; deletion of Brd1 in haematopoietic progenitors causes variegated Cd8 expression, demonstrating that Brd1-mediated H3K14ac is an epigenetic mark that promotes transcription machinery recruitment to Cd8 enhancers.","method":"Conditional knockout mouse model, ChIP analysis of Brd1 occupancy and H3K14ac at Cd8 enhancers, co-immunoprecipitation of Brd1-Hbo1 complex in thymocytes","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, locus-specific ChIP, and conditional KO with defined cellular phenotype, all in one study","pmids":["25519988"],"is_preprint":false},{"year":2017,"finding":"A short N-terminal region of BRPF2 (BRD1) is sufficient to bind the HBO1 MYST domain and potentiate its HAT activity toward H3K14 on free histone H3, H4, and nucleosomal H3; the crystal structure of the HBO1 MYST domain in complex with this BRPF2 segment identified key interface residues responsible for the interaction.","method":"Crystal structure of HBO1-BRPF2 complex, in vitro HAT activity assays with truncation mutants, mutagenesis of interface residues, cell biological validation","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus in vitro reconstitution HAT assay plus mutagenesis plus cell biology in a single rigorous study","pmids":["28334966"],"is_preprint":false},{"year":2012,"finding":"The second PHD finger (PHD2) within the PZPM motif of human BRPF2 (BRD1) adopts an atypical two-strand β-sheet structure distinct from canonical PHD fingers, and this domain can bind DNA non-specifically via an evolutionarily conserved positively charged surface.","method":"NMR solution structure determination, in vitro DNA-binding assays","journal":"Journal of structural biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — NMR structure with binding assay but single lab, no mutagenesis validation of binding surface","pmids":["22820306"],"is_preprint":false},{"year":2021,"finding":"The BRPF2 (BRD1) PWWP domain binds double-stranded DNA without sequence selectivity, and its crystal structure in complex with a 12-mer dsDNA reveals that the domain interacts with the major groove of DNA—a binding mode distinct from the minor-groove engagement observed in the HDGF family of PWWP domains.","method":"Crystal structure of BRPF2 PWWP domain in complex with dsDNA, family-wide dsDNA binding assays","journal":"Biochimica et biophysica acta. Gene regulatory mechanisms","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure with binding assay validation; single lab but orthogonal structural and biochemical methods","pmids":["33556623"],"is_preprint":false},{"year":2016,"finding":"BRD1 interacts with chromatin remodeling proteins (e.g., PBRM1) and histone modifiers (e.g., MYST2/HBO1, SUV420H1) as identified by Co-IP/mass spectrometry; BRD1 isoforms (BRD1-S and BRD1-L) show isoform-specific protein interactions and primarily bind near transcription start sites to regulate expression of numerous genes including those involved in brain development.","method":"Co-immunoprecipitation followed by mass spectrometry, ChIP-seq in stable human cell lines expressing epitope-tagged BRD1-S and BRD1-L, microarray gene expression profiling","journal":"Genome medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP/MS interactome plus ChIP-seq, single lab but two orthogonal methods with functional expression data","pmids":["27142060"],"is_preprint":false},{"year":2016,"finding":"Heterozygous deletion of Brd1 in mice causes cerebral histone H3K14 hypoacetylation, striatal dopamine/serotonin abnormalities, cortical excitation-inhibition imbalance with loss of parvalbumin interneurons, and schizophrenia-relevant behavioral phenotypes; RNA-sequencing revealed differential expression of schizophrenia GWAS risk genes including Cacna1c, Drd2, and Tcf4.","method":"Brd1+/- mouse model, behavioral testing, electrophysiology, RNA-sequencing of cortical and striatal micropunches, immunohistochemistry for parvalbumin, histone modification analysis","journal":"Biological psychiatry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined KO with multiple orthogonal readouts (behavior, electrophysiology, transcriptomics, histone marks), single lab","pmids":["27837920"],"is_preprint":false},{"year":2016,"finding":"BRPF2 (BRD1) depletion in mouse embryonic stem cells reduces global H3K14 acetylation and impairs retinoic acid-induced differentiation; co-immunoprecipitation in differentiated ESCs revealed a physical interaction between BRPF2 and the HAT MOZ, suggesting BRPF2-MOZ complexes regulate ESC differentiation via H3K14ac.","method":"siRNA knockdown of BRPF2 in ESCs, alkaline phosphatase activity assay, co-immunoprecipitation, western blot for H3K14ac","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP plus KD phenotype across multiple orthogonal readouts, single lab","pmids":["27256846"],"is_preprint":false},{"year":2006,"finding":"BRD1 protein is localized to the nucleus, perikaryal cytosol, and proximal dendrites of neurons in adult rat, rabbit, and human CNS as detected by immunohistochemistry; quantitative mRNA analysis in developing fetal pig brain showed high early embryonic expression with intense nuclear staining of neuroepithelial cells, shifting to less nuclear staining in more mature neurons.","method":"Immunohistochemistry on adult CNS sections, quantitative mRNA analysis in developing fetal pig brain","journal":"Molecular psychiatry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization by IHC, single lab, no direct functional consequence linked to the localization","pmids":["16924267"],"is_preprint":false},{"year":1999,"finding":"The BRD1 (BRL) gene encodes a nuclear protein of ~120 kDa that contains a bromodomain, a cysteine-rich region related to the AF10/AF17 leukaemia proteins, four LXXLL motifs, and predicted nuclear localization signals; a monoclonal antibody confirmed nuclear localization within spermatocytes and widespread expression.","method":"cDNA cloning, protein sequence analysis, monoclonal antibody immunostaining, expression analysis by Northern/Western blot","journal":"Oncogene","confidence":"Low","confidence_rationale":"Tier 3 / Weak — initial cloning and localization study, single lab, no functional mechanistic follow-up","pmids":["10602503"],"is_preprint":false},{"year":2024,"finding":"NIT2 interacts with BRD1 to inhibit HBO1-mediated H3K14 acetylation; upon 5-FU stimulation, Src phosphorylates NIT2 at Y49, promoting NIT2 dissociation from BRD1 and its autophagic degradation, which causes BRD1 to form phase-separated condensates and bind histone H3, increasing H3K14ac and RELA-dependent OXPHOS gene expression, thereby driving 5-FU chemoresistance in gastric cancer.","method":"CRISPR-Cas9 screen, Co-IP, proximity ligation assay, patient-derived organoids, xenograft tumors, biochemical fractionation, phase separation assays, Src kinase assay","journal":"Science translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods including Co-IP, kinase assay, and phase separation assays in one study, single lab","pmids":["39565874"],"is_preprint":false},{"year":2017,"finding":"Benzoisoquinolinedione compounds (including BAY-299) selectively inhibit the bromodomain of BRPF2 (BRD1) with IC50 of 67 nM, and cellular activity was confirmed using a BRPF2-histone H3.3/H4 interaction assay, demonstrating that the BRPF2 bromodomain functions as a reader of acetylated lysine marks on histones.","method":"High-throughput biochemical screening, SAR-guided medicinal chemistry, selectivity profiling across bromodomains, cellular BRPF2-histone interaction assay","journal":"Journal of medicinal chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical inhibitor assay with cellular validation, multiple selectivity controls, single lab","pmids":["28402630"],"is_preprint":false}],"current_model":"BRD1 (BRPF2) is a scaffold/regulatory subunit of HBO1 (MYST2) histone acetyltransferase complexes, where its N-terminal region directly contacts the HBO1 MYST domain (crystal structure solved) to potentiate H3K14 acetylation on nucleosomes; BRD1 bridges HBO1 to the activator ING4, and the complex is the major H3K14 HAT required for transcriptional activation of developmental regulator genes in erythropoiesis, T-cell development, and ESC differentiation, while BRD1's bromodomain acts as an acetyl-lysine reader and its PWWP and PHD domains mediate non-sequence-specific DNA binding; loss of Brd1 causes brain-relevant H3K14 hypoacetylation and schizophrenia-related behavioral and neurochemical phenotypes in mice."},"narrative":{"mechanistic_narrative":"BRD1 (BRPF2) is a scaffolding and regulatory subunit of MYST-family histone acetyltransferase complexes that delivers histone H3 lysine 14 acetylation (H3K14ac) at developmental gene loci, coupling chromatin modification to transcriptional activation across erythropoiesis, T-cell development, and embryonic stem cell differentiation [PMID:21753189, PMID:25519988, PMID:27256846]. A short N-terminal segment of BRD1 directly engages the HBO1 (MYST2) MYST domain to potentiate its acetyltransferase activity toward free and nucleosomal H3, an interaction defined at residue resolution by the HBO1–BRPF2 crystal structure [PMID:28334966]; within the complex BRD1 also bridges HBO1 to the activator ING4 and is the major activity responsible for global H3K14ac in erythroblasts, where its loss impairs fetal liver erythropoiesis [PMID:21753189]. BRD1 likewise interacts with the related HAT MOZ to control H3K14ac-dependent ESC differentiation [PMID:27256846], and recruits to gene enhancers and transcription start sites to drive expression of lineage regulators [PMID:25519988, PMID:27142060]. Chromatin engagement is mediated by multiple reader/binding modules: a bromodomain that reads acetyl-lysine marks on histone H3.3/H4 [PMID:28402630], and PWWP and atypical PHD domains that bind double-stranded DNA non-specifically, the PWWP domain engaging the DNA major groove [PMID:22820306, PMID:33556623]. BRD1 activity is restrained by NIT2, whose Src-dependent phosphorylation and degradation releases BRD1 to form phase-separated condensates that bind histone H3 and elevate H3K14ac, linking the complex to RELA-dependent transcription and chemoresistance [PMID:39565874]. Heterozygous loss of Brd1 in mice causes cerebral H3K14 hypoacetylation and schizophrenia-relevant behavioral, neurochemical, and cortical interneuron phenotypes, with dysregulation of schizophrenia risk genes [PMID:27837920].","teleology":[{"year":1999,"claim":"The founding question was what BRD1 encodes; cloning established it as a nuclear bromodomain-containing protein with a cysteine-rich region and LXXLL motifs, framing it as a chromatin-associated factor.","evidence":"cDNA cloning, protein sequence analysis, and antibody immunostaining showing nuclear localization","pmids":["10602503"],"confidence":"Low","gaps":["Initial characterization with no functional or enzymatic assignment","No identified protein partners or chromatin targets"]},{"year":2006,"claim":"Tissue-level expression mapping addressed where BRD1 acts, placing the protein in neuronal nuclei and CNS development before any molecular function was known.","evidence":"Immunohistochemistry across mammalian CNS and mRNA quantification in developing fetal pig brain","pmids":["16924267"],"confidence":"Low","gaps":["Localization not linked to a molecular activity","No mechanistic consequence of CNS expression defined"]},{"year":2011,"claim":"The defining mechanistic question — what enzymatic complex BRD1 belongs to — was answered by showing it bridges HBO1 to ING4 and is required for global H3K14 acetylation in vivo, establishing BRD1 as a HAT-complex subunit controlling erythropoiesis.","evidence":"Reciprocal Co-IP, genome-wide ChIP in erythroblasts, and conditional knockout mouse with Gata1 rescue","pmids":["21753189"],"confidence":"High","gaps":["Structural basis of the HBO1 interaction not yet defined","Direct contribution of BRD1 domains to substrate selectivity unresolved"]},{"year":2012,"claim":"How BRD1 contacts chromatin DNA was probed by structure determination of its PHD2 domain, revealing an atypical fold that binds DNA non-specifically via a conserved basic surface.","evidence":"NMR solution structure and in vitro DNA-binding assays","pmids":["22820306"],"confidence":"Medium","gaps":["No mutagenesis validation of the binding surface","Functional role of DNA binding in cells untested"]},{"year":2014,"claim":"Whether BRD1-mediated H3K14ac functions as an activating mark at specific loci was established by showing BRD1 occupies Cd8 enhancers and is required for stable Cd8 expression in T-cell development.","evidence":"Conditional KO mouse, locus-specific ChIP for occupancy and H3K14ac, and Co-IP of the Brd1-Hbo1 complex in thymocytes","pmids":["25519988"],"confidence":"High","gaps":["Mechanism linking H3K14ac to transcription machinery recruitment not directly demonstrated","Generalizability beyond Cd8 enhancers not established here"]},{"year":2016,"claim":"The interactome and genomic targeting of BRD1 were broadened, identifying isoform-specific partners (PBRM1, MYST2, SUV420H1) and TSS-proximal binding regulating brain-development genes.","evidence":"Co-IP/mass spectrometry interactome plus ChIP-seq and expression profiling of tagged BRD1-S and BRD1-L isoforms","pmids":["27142060"],"confidence":"Medium","gaps":["Direct versus indirect nature of some interactions not resolved","Functional consequences of isoform-specific interactions not dissected"]},{"year":2016,"claim":"BRD1's role in pluripotency was addressed by showing its depletion lowers H3K14ac and blocks RA-induced ESC differentiation, and that it partners not only with HBO1 but also with MOZ.","evidence":"siRNA knockdown in ESCs, differentiation assay, Co-IP, and H3K14ac western blot","pmids":["27256846"],"confidence":"Medium","gaps":["Single Co-IP for the MOZ interaction without reciprocal validation","Whether MOZ and HBO1 complexes are functionally distinct in ESCs unresolved"]},{"year":2016,"claim":"The neurological relevance of BRD1 was tested in vivo, linking heterozygous loss to H3K14 hypoacetylation, cortical interneuron and neurochemical deficits, and dysregulation of schizophrenia risk genes.","evidence":"Brd1+/- mouse with behavior, electrophysiology, immunohistochemistry, histone marks, and RNA-seq of brain micropunches","pmids":["27837920"],"confidence":"Medium","gaps":["Causal chain from H3K14 hypoacetylation to behavior not directly demonstrated","No human genetic causation established within this study"]},{"year":2017,"claim":"The structural and biochemical basis of HBO1 activation was resolved by crystallizing the HBO1 MYST domain with a minimal BRPF2 segment and showing this segment is sufficient to potentiate H3K14 HAT activity.","evidence":"Crystal structure, in vitro HAT assays with truncation and interface mutants, and cell validation","pmids":["28334966"],"confidence":"High","gaps":["Structure limited to the BRPF2 N-terminal segment, not full-length BRD1","Role of BRD1 reader domains in the assembled complex not captured"]},{"year":2017,"claim":"The function of the BRD1 bromodomain as an acetyl-lysine reader was confirmed pharmacologically, with selective inhibitors blocking BRPF2 binding to acetylated H3.3/H4.","evidence":"Biochemical inhibitor screening, SAR, bromodomain selectivity profiling, and cellular BRPF2-histone interaction assay","pmids":["28402630"],"confidence":"Medium","gaps":["Physiological acetyl-lysine targets read by the bromodomain not mapped","Cellular phenotype of bromodomain inhibition not characterized here"]},{"year":2021,"claim":"How the BRD1 PWWP domain engages chromatin DNA was clarified structurally, showing major-groove dsDNA binding distinct from HDGF-family PWWP domains.","evidence":"Crystal structure of the PWWP domain bound to dsDNA and family-wide binding assays","pmids":["33556623"],"confidence":"High","gaps":["In vivo contribution of PWWP DNA binding to BRD1 targeting untested","Coordination with PHD and bromodomain in chromatin engagement unresolved"]},{"year":2024,"claim":"A regulatory switch controlling BRD1 activity was uncovered: NIT2 normally inhibits HBO1-mediated H3K14ac through BRD1, and Src-driven NIT2 degradation releases BRD1 to form condensates that boost H3K14ac and RELA-dependent transcription, driving chemoresistance.","evidence":"CRISPR screen, Co-IP, proximity ligation, kinase assay, phase-separation assays, organoids, and xenografts","pmids":["39565874"],"confidence":"Medium","gaps":["Physiological relevance of BRD1 phase separation beyond chemoresistance unresolved","Single-lab study without independent replication of the condensate model"]},{"year":null,"claim":"How BRD1's multiple chromatin-reading modules (bromodomain, PWWP, PHD) are integrated for genome-wide targeting, and whether HBO1- versus MOZ-containing complexes have distinct in vivo functions, remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No full-length BRD1 structure within an assembled HAT complex","Division of labor between HBO1 and MOZ complexes not resolved","Rules governing locus-specific recruitment not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[2,11]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[3,4]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,2]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,5]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[8,9]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[1,0]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,5]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[0,7]}],"complexes":["HBO1 (MYST2) histone acetyltransferase complex","MOZ histone acetyltransferase complex"],"partners":["HBO1","MYST2","ING4","MOZ","PBRM1","SUV420H1","NIT2","RELA"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O95696","full_name":"Bromodomain-containing protein 1","aliases":["BR140-like protein","Bromodomain and PHD finger-containing protein 2"],"length_aa":1058,"mass_kda":119.5,"function":"Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, that acts as a regulator of hematopoiesis (PubMed:16387653, PubMed:21753189, PubMed:21880731). Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac), thereby promoting erythroid differentiation (PubMed:21753189)","subcellular_location":"Nucleus; Chromosome","url":"https://www.uniprot.org/uniprotkb/O95696/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/BRD1","classification":"Not Classified","n_dependent_lines":123,"n_total_lines":1208,"dependency_fraction":0.10182119205298014},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"HMGN5","stoichiometry":0.2},{"gene":"NUMA1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/BRD1","total_profiled":1310},"omim":[{"mim_id":"604589","title":"BROMODOMAIN-CONTAINING PROTEIN 1; BRD1","url":"https://www.omim.org/entry/604589"},{"mim_id":"602410","title":"BROMODOMAIN- AND PHD FINGER-CONTAINING PROTEIN; BRPF1","url":"https://www.omim.org/entry/602410"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear speckles","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/BRD1"},"hgnc":{"alias_symbol":["BRL","BRPF2"],"prev_symbol":[]},"alphafold":{"accession":"O95696","domains":[{"cath_id":"-","chopping":"146-207_449-492","consensus_level":"medium","plddt":87.3679,"start":146,"end":492},{"cath_id":"3.30.40","chopping":"256-382","consensus_level":"high","plddt":89.9211,"start":256,"end":382},{"cath_id":"1.20.920.10","chopping":"554-757","consensus_level":"medium","plddt":93.066,"start":554,"end":757},{"cath_id":"2.30.30.140","chopping":"925-1046","consensus_level":"high","plddt":86.8807,"start":925,"end":1046},{"cath_id":"1.10.287","chopping":"883-915","consensus_level":"medium","plddt":61.7824,"start":883,"end":915}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O95696","model_url":"https://alphafold.ebi.ac.uk/files/AF-O95696-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O95696-F1-predicted_aligned_error_v6.png","plddt_mean":71.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=BRD1","jax_strain_url":"https://www.jax.org/strain/search?query=BRD1"},"sequence":{"accession":"O95696","fasta_url":"https://rest.uniprot.org/uniprotkb/O95696.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O95696/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O95696"}},"corpus_meta":[{"pmid":"16125895","id":"PMC_16125895","title":"In vitro toxicity of nanoparticles in BRL 3A rat liver cells.","date":"2005","source":"Toxicology in vitro : an international journal published in association with BIBRA","url":"https://pubmed.ncbi.nlm.nih.gov/16125895","citation_count":1149,"is_preprint":false},{"pmid":"9454824","id":"PMC_9454824","title":"Identification of high-affinity binding sites for the insulin sensitizer rosiglitazone (BRL-49653) in rodent and human adipocytes using a radioiodinated ligand for peroxisomal proliferator-activated receptor gamma.","date":"1998","source":"The Journal of pharmacology and experimental therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/9454824","citation_count":213,"is_preprint":false},{"pmid":"2851311","id":"PMC_2851311","title":"The anti-emetic potential of the 5-hydroxytryptamine3 receptor antagonist BRL 43694.","date":"1988","source":"British journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/2851311","citation_count":202,"is_preprint":false},{"pmid":"2540014","id":"PMC_2540014","title":"Selective and functional 5-hydroxytryptamine3 receptor antagonism by BRL 43694 (granisetron).","date":"1989","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/2540014","citation_count":197,"is_preprint":false},{"pmid":"3631945","id":"PMC_3631945","title":"Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxy-methylbut-1-yl)guanine (BRL 39123) in cell culture.","date":"1987","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/3631945","citation_count":175,"is_preprint":false},{"pmid":"21753189","id":"PMC_21753189","title":"The Hbo1-Brd1/Brpf2 complex is responsible for global acetylation of H3K14 and required for fetal liver erythropoiesis.","date":"2011","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/21753189","citation_count":173,"is_preprint":false},{"pmid":"32659578","id":"PMC_32659578","title":"Exposure to copper oxide nanoparticles triggers oxidative stress and endoplasmic reticulum (ER)-stress induced toxicology and apoptosis in male rat liver and BRL-3A cell.","date":"2020","source":"Journal of hazardous materials","url":"https://pubmed.ncbi.nlm.nih.gov/32659578","citation_count":151,"is_preprint":false},{"pmid":"9568706","id":"PMC_9568706","title":"BRL 49653 blocks the lipolytic actions of tumor necrosis factor-alpha: a potential new insulin-sensitizing mechanism for thiazolidinediones.","date":"1998","source":"Diabetes","url":"https://pubmed.ncbi.nlm.nih.gov/9568706","citation_count":145,"is_preprint":false},{"pmid":"9303567","id":"PMC_9303567","title":"SB-216641 and BRL-15572--compounds to pharmacologically discriminate h5-HT1B and h5-HT1D receptors.","date":"1997","source":"Naunyn-Schmiedeberg's archives of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/9303567","citation_count":143,"is_preprint":false},{"pmid":"15371556","id":"PMC_15371556","title":"Discovery of BRL 50481 [3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene], a selective inhibitor of phosphodiesterase 7: in vitro studies in human monocytes, lung macrophages, and CD8+ T-lymphocytes.","date":"2004","source":"Molecular pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/15371556","citation_count":142,"is_preprint":false},{"pmid":"2559349","id":"PMC_2559349","title":"The 5-HT3 receptor ligand, [3H]BRL 43694, binds to presynaptic sites in the nucleus tractus solitarius of the rat.","date":"1989","source":"Neuropharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/2559349","citation_count":136,"is_preprint":false},{"pmid":"22292043","id":"PMC_22292043","title":"Brd1 gene in maize encodes a brassinosteroid C-6 oxidase.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22292043","citation_count":125,"is_preprint":false},{"pmid":"7657033","id":"PMC_7657033","title":"Repeat treatment of obese mice with BRL 49653, a new potent insulin sensitizer, enhances insulin action in white adipocytes. Association with increased insulin binding and cell-surface GLUT4 as measured by photoaffinity labeling.","date":"1995","source":"Diabetes","url":"https://pubmed.ncbi.nlm.nih.gov/7657033","citation_count":125,"is_preprint":false},{"pmid":"3594084","id":"PMC_3594084","title":"Increased gut cholinergic activity and antagonism of 5-hydroxytryptamine M-receptors by BRL 24924: potential clinical importance of BRL 24924.","date":"1987","source":"British journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/3594084","citation_count":121,"is_preprint":false},{"pmid":"2589844","id":"PMC_2589844","title":"Selection of an oral prodrug (BRL 42810; famciclovir) for the antiherpesvirus agent BRL 39123 [9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine; penciclovir].","date":"1989","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/2589844","citation_count":115,"is_preprint":false},{"pmid":"9258278","id":"PMC_9258278","title":"The insulin sensitizer, BRL 49653, reduces systemic fatty acid supply and utilization and tissue lipid availability in the rat.","date":"1997","source":"Metabolism: clinical and experimental","url":"https://pubmed.ncbi.nlm.nih.gov/9258278","citation_count":114,"is_preprint":false},{"pmid":"2426267","id":"PMC_2426267","title":"Purification and amino-terminal sequence of an insulin-like growth factor-binding protein secreted by rat liver BRL-3A cells.","date":"1986","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2426267","citation_count":109,"is_preprint":false},{"pmid":"2541655","id":"PMC_2541655","title":"Mode of action of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) against herpes simplex virus in MRC-5 cells.","date":"1989","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/2541655","citation_count":101,"is_preprint":false},{"pmid":"2422012","id":"PMC_2422012","title":"Insulin-like growth factor carrier proteins in neonatal and adult rat serum are immunologically different: demonstration using a new radioimmunoassay for the carrier protein from BRL-3A rat liver cells.","date":"1986","source":"Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/2422012","citation_count":101,"is_preprint":false},{"pmid":"25549941","id":"PMC_25549941","title":"Individual and combined cytotoxic effects of aflatoxin B1, zearalenone, deoxynivalenol and fumonisin B1 on BRL 3A rat liver cells.","date":"2014","source":"Toxicon : official journal of the International Society on Toxinology","url":"https://pubmed.ncbi.nlm.nih.gov/25549941","citation_count":95,"is_preprint":false},{"pmid":"6152555","id":"PMC_6152555","title":"Treatment of obesity with thermogenic beta-adrenoceptor agonists: studies on BRL 26830A in rodents.","date":"1984","source":"International journal of obesity","url":"https://pubmed.ncbi.nlm.nih.gov/6152555","citation_count":90,"is_preprint":false},{"pmid":"2542062","id":"PMC_2542062","title":"BRL 24924: a potent agonist at a non-classical 5-HT receptor positively coupled with adenylate cyclase in colliculi neurons.","date":"1989","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/2542062","citation_count":88,"is_preprint":false},{"pmid":"2782410","id":"PMC_2782410","title":"Blockade of 5-HT-mediated enteric slow EPSPs by BRL 24924: gastrokinetic effects.","date":"1989","source":"The American journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/2782410","citation_count":76,"is_preprint":false},{"pmid":"3364954","id":"PMC_3364954","title":"Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxymethylbut-1-yl) guanine (BRL 39123) in animals.","date":"1988","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/3364954","citation_count":75,"is_preprint":false},{"pmid":"8954968","id":"PMC_8954968","title":"The thiazolidinedione insulin sensitiser, BRL 49653, increases the expression of PPAR-gamma and aP2 in adipose tissue of high-fat-fed rats.","date":"1996","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/8954968","citation_count":74,"is_preprint":false},{"pmid":"1668810","id":"PMC_1668810","title":"Cisplatin-evoked induction of c-fos protein in the brainstem of the ferret: the effect of cervical vagotomy and the anti-emetic 5-HT3 receptor antagonist granisetron (BRL 43694).","date":"1991","source":"Brain research","url":"https://pubmed.ncbi.nlm.nih.gov/1668810","citation_count":72,"is_preprint":false},{"pmid":"1345889","id":"PMC_1345889","title":"BRL 35135, a potent and selective atypical beta-adrenoceptor agonist.","date":"1992","source":"The American journal of clinical nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/1345889","citation_count":70,"is_preprint":false},{"pmid":"9303568","id":"PMC_9303568","title":"Effects of selective h5-HT1B (SB-216641) and h5-HT1D (BRL-15572) receptor ligands on guinea-pig and human 5-HT auto- and heteroreceptors.","date":"1997","source":"Naunyn-Schmiedeberg's archives of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/9303568","citation_count":68,"is_preprint":false},{"pmid":"3882697","id":"PMC_3882697","title":"Biosynthesis of rat insulin-like growth factor II. I. Immunochemical demonstration of a approximately 20-kilodalton biosynthetic precursor of rat insulin-like growth factor II in metabolically labeled BRL-3A rat liver cells.","date":"1985","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/3882697","citation_count":66,"is_preprint":false},{"pmid":"16924267","id":"PMC_16924267","title":"Evidence implicating BRD1 with brain development and susceptibility to both schizophrenia and bipolar affective disorder.","date":"2006","source":"Molecular psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/16924267","citation_count":65,"is_preprint":false},{"pmid":"3405317","id":"PMC_3405317","title":"Actions of BRL 34915 (Cromakalim) upon convulsive discharges in guinea pig hippocampal slices.","date":"1988","source":"Naunyn-Schmiedeberg's archives of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/3405317","citation_count":63,"is_preprint":false},{"pmid":"1504756","id":"PMC_1504756","title":"Characterization of potassium currents modulated by BRL 38227 in rat portal vein.","date":"1992","source":"British journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/1504756","citation_count":58,"is_preprint":false},{"pmid":"1504734","id":"PMC_1504734","title":"Comparison of the actions of acetylcholine and BRL 38227 in the guinea-pig coronary artery.","date":"1992","source":"British journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/1504734","citation_count":57,"is_preprint":false},{"pmid":"31491605","id":"PMC_31491605","title":"Mono-2-ethylhexyl phthalate (MEHP) promoted lipid accumulation via JAK2/STAT5 and aggravated oxidative stress in BRL-3A cells.","date":"2019","source":"Ecotoxicology and environmental safety","url":"https://pubmed.ncbi.nlm.nih.gov/31491605","citation_count":49,"is_preprint":false},{"pmid":"19693800","id":"PMC_19693800","title":"Support of association between BRD1 and both schizophrenia and bipolar affective disorder.","date":"2010","source":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/19693800","citation_count":48,"is_preprint":false},{"pmid":"28402630","id":"PMC_28402630","title":"Benzoisoquinolinediones as Potent and Selective Inhibitors of BRPF2 and TAF1/TAF1L Bromodomains.","date":"2017","source":"Journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28402630","citation_count":48,"is_preprint":false},{"pmid":"7831418","id":"PMC_7831418","title":"BRL 46470A: a highly potent, selective and long acting 5-HT3 receptor antagonist with anxiolytic-like properties.","date":"1993","source":"Psychopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/7831418","citation_count":48,"is_preprint":false},{"pmid":"31185235","id":"PMC_31185235","title":"Allicin alleviates acrylamide-induced oxidative stress in BRL-3A cells.","date":"2019","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/31185235","citation_count":46,"is_preprint":false},{"pmid":"23577223","id":"PMC_23577223","title":"Oxidative stress and mitogen-activated protein kinase pathways involved in cadmium-induced BRL 3A cell apoptosis.","date":"2013","source":"Oxidative medicine and cellular longevity","url":"https://pubmed.ncbi.nlm.nih.gov/23577223","citation_count":45,"is_preprint":false},{"pmid":"8413836","id":"PMC_8413836","title":"BRL 46470 potently antagonizes neural responses activated by 5-HT3 receptors.","date":"1993","source":"Neuropharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/8413836","citation_count":44,"is_preprint":false},{"pmid":"9374677","id":"PMC_9374677","title":"Reversal of chronic alterations of skeletal muscle protein kinase C from fat-fed rats by BRL-49653.","date":"1997","source":"The American journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/9374677","citation_count":42,"is_preprint":false},{"pmid":"16368690","id":"PMC_16368690","title":"The Brl domain in Sec63p is required for assembly of functional endoplasmic reticulum translocons.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16368690","citation_count":42,"is_preprint":false},{"pmid":"9826550","id":"PMC_9826550","title":"The effects of the beta3-adrenoceptor agonist BRL 35135 on UCP isoform mRNA expression.","date":"1998","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/9826550","citation_count":42,"is_preprint":false},{"pmid":"33781805","id":"PMC_33781805","title":"Rosmarinic acid attenuates acrylamide induced apoptosis of BRL-3A cells by inhibiting oxidative stress and endoplasmic reticulum stress.","date":"2021","source":"Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association","url":"https://pubmed.ncbi.nlm.nih.gov/33781805","citation_count":41,"is_preprint":false},{"pmid":"2181144","id":"PMC_2181144","title":"Comparative study of the effects of cromakalim (BRL 34915) and diazoxide on membrane potential, [Ca2+]i and ATP-sensitive potassium currents in insulin-secreting cells.","date":"1990","source":"The Journal of membrane biology","url":"https://pubmed.ncbi.nlm.nih.gov/2181144","citation_count":40,"is_preprint":false},{"pmid":"22820306","id":"PMC_22820306","title":"Solution structure of an atypical PHD finger in BRPF2 and its interaction with DNA.","date":"2012","source":"Journal of structural biology","url":"https://pubmed.ncbi.nlm.nih.gov/22820306","citation_count":39,"is_preprint":false},{"pmid":"29529605","id":"PMC_29529605","title":"Acetic Acid Influences BRL-3A Cell Lipid Metabolism via the AMPK Signalling Pathway.","date":"2018","source":"Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/29529605","citation_count":39,"is_preprint":false},{"pmid":"25519988","id":"PMC_25519988","title":"Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development.","date":"2014","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/25519988","citation_count":39,"is_preprint":false},{"pmid":"12738895","id":"PMC_12738895","title":"Neuroprotective kappa-opioid receptor agonist BRL 52537 attenuates ischemia-evoked nitric oxide production in vivo in rats.","date":"2003","source":"Stroke","url":"https://pubmed.ncbi.nlm.nih.gov/12738895","citation_count":38,"is_preprint":false},{"pmid":"26969466","id":"PMC_26969466","title":"Hsp70 suppresses apoptosis of BRL cells by regulating the expression of Bcl-2, cytochrome C, and caspase 8/3.","date":"2016","source":"In vitro cellular & developmental biology. Animal","url":"https://pubmed.ncbi.nlm.nih.gov/26969466","citation_count":38,"is_preprint":false},{"pmid":"6440479","id":"PMC_6440479","title":"In vitro antibacterial properties of BRL 36650, a novel 6 alpha-substituted penicillin.","date":"1984","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/6440479","citation_count":38,"is_preprint":false},{"pmid":"9614218","id":"PMC_9614218","title":"Specific activation of the nuclear receptors PPARgamma and RORA by the antidiabetic thiazolidinedione BRL 49653 and the antiarthritic thiazolidinedione derivative CGP 52608.","date":"1998","source":"Molecular pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/9614218","citation_count":37,"is_preprint":false},{"pmid":"3393236","id":"PMC_3393236","title":"Enhancement of muscle blood cell flux and pO2 by cromakalim (BRL 34915) and other compounds enhancing membrane K+ conductance, but not by Ca2+ antagonists or hydralazine, in an animal model of occlusive arterial disease.","date":"1988","source":"Naunyn-Schmiedeberg's archives of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/3393236","citation_count":37,"is_preprint":false},{"pmid":"2473889","id":"PMC_2473889","title":"Expression of the BRL-3A insulin-like growth factor binding protein (rBP-30) in the rat central nervous system.","date":"1989","source":"Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/2473889","citation_count":34,"is_preprint":false},{"pmid":"14633559","id":"PMC_14633559","title":"Kappa-opioid receptor selectivity for ischemic neuroprotection with BRL 52537 in rats.","date":"2003","source":"Anesthesia and analgesia","url":"https://pubmed.ncbi.nlm.nih.gov/14633559","citation_count":34,"is_preprint":false},{"pmid":"31671698","id":"PMC_31671698","title":"Screening of the Hepatotoxic Components in Fructus Gardeniae and Their Effects on Rat Liver BRL-3A Cells.","date":"2019","source":"Molecules (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/31671698","citation_count":34,"is_preprint":false},{"pmid":"2257436","id":"PMC_2257436","title":"Zacopride and BRL 24924 induce an increase in EEG-energy in rats.","date":"1990","source":"British journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/2257436","citation_count":33,"is_preprint":false},{"pmid":"27187187","id":"PMC_27187187","title":"Amphipathic silica nanoparticles induce cytotoxicity through oxidative stress mediated and p53 dependent apoptosis pathway in human liver cell line HL-7702 and rat liver cell line BRL-3A.","date":"2016","source":"Colloids and surfaces. B, Biointerfaces","url":"https://pubmed.ncbi.nlm.nih.gov/27187187","citation_count":32,"is_preprint":false},{"pmid":"23873220","id":"PMC_23873220","title":"Oxidative stress increased hepatotoxicity induced by nano-titanium dioxide in BRL-3A cells and Sprague-Dawley rats.","date":"2013","source":"Journal of applied toxicology : JAT","url":"https://pubmed.ncbi.nlm.nih.gov/23873220","citation_count":32,"is_preprint":false},{"pmid":"8840342","id":"PMC_8840342","title":"Effects of anxiety and memory of systemic and intra-amygdala injection of 5-HT3 receptor antagonist BRL 46470A.","date":"1996","source":"Neuropsychobiology","url":"https://pubmed.ncbi.nlm.nih.gov/8840342","citation_count":31,"is_preprint":false},{"pmid":"28334966","id":"PMC_28334966","title":"Structural and mechanistic insights into regulation of HBO1 histone acetyltransferase activity by BRPF2.","date":"2017","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/28334966","citation_count":29,"is_preprint":false},{"pmid":"27142060","id":"PMC_27142060","title":"Identification of the BRD1 interaction network and its impact on mental disorder risk.","date":"2016","source":"Genome medicine","url":"https://pubmed.ncbi.nlm.nih.gov/27142060","citation_count":28,"is_preprint":false},{"pmid":"2963005","id":"PMC_2963005","title":"Anti-spasmogenic and spasmolytic effects of BRL 34915: a comparison with nifedipine and nicorandil.","date":"1987","source":"Journal of autonomic pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/2963005","citation_count":28,"is_preprint":false},{"pmid":"18625072","id":"PMC_18625072","title":"The PPARgamma-selective ligand BRL-49653 differentially regulates the fate choices of rat calvaria versus rat bone marrow stromal cell populations.","date":"2008","source":"BMC developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/18625072","citation_count":28,"is_preprint":false},{"pmid":"1345886","id":"PMC_1345886","title":"The antidiabetic beta 3-adrenoceptor agonist BRL 26830A works by release of endogenous insulin.","date":"1992","source":"The American journal of clinical nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/1345886","citation_count":27,"is_preprint":false},{"pmid":"19714315","id":"PMC_19714315","title":"Expression of BrD1, a plant defensin from Brassica rapa, confers resistance against brown planthopper (Nilaparvata lugens) in transgenic rices.","date":"2009","source":"Molecules and cells","url":"https://pubmed.ncbi.nlm.nih.gov/19714315","citation_count":26,"is_preprint":false},{"pmid":"36034823","id":"PMC_36034823","title":"Alleviating effect of quercetin on cadmium-induced oxidative damage and apoptosis by activating the Nrf2-keap1 pathway in BRL-3A cells.","date":"2022","source":"Frontiers in pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/36034823","citation_count":26,"is_preprint":false},{"pmid":"2476983","id":"PMC_2476983","title":"The 34 kilodalton insulin-like growth factor binding proteins in human cerebrospinal fluid and the A673 rhabdomyosarcoma cell line are human homologues of the rat BRL-3A binding protein.","date":"1989","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/2476983","citation_count":26,"is_preprint":false},{"pmid":"19181295","id":"PMC_19181295","title":"Effects of the beta3-adrenergic agonist BRL 37344 on endothelial nitric oxide synthase phosphorylation and force of contraction in human failing myocardium.","date":"2008","source":"Journal of cardiac failure","url":"https://pubmed.ncbi.nlm.nih.gov/19181295","citation_count":26,"is_preprint":false},{"pmid":"16727807","id":"PMC_16727807","title":"Culture of in vitro fertilized bovine embryos with bovine oviductal epithelial cells, Buffalo rat liver (BRL) cells, or BRL-cell-conditioned medium.","date":"1996","source":"Theriogenology","url":"https://pubmed.ncbi.nlm.nih.gov/16727807","citation_count":26,"is_preprint":false},{"pmid":"1649417","id":"PMC_1649417","title":"An ethological study of the effects of buspirone and the 5-HT3 receptor antagonist, BRL 43694 (granisetron) on behaviour during social interactions in female and male mice.","date":"1991","source":"Neuropharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/1649417","citation_count":25,"is_preprint":false},{"pmid":"30816537","id":"PMC_30816537","title":"ACC1 is overexpressed in liver cancers and contributes to the proliferation of human hepatoma Hep G2 cells and the rat liver cell line BRL 3A.","date":"2019","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/30816537","citation_count":24,"is_preprint":false},{"pmid":"1356251","id":"PMC_1356251","title":"Effects of acute administration of the 5-HT3 receptor antagonist, BRL 46470A, on the behaviour of mice in a two compartment light-dark box and during social interactions in their home cage and an unfamiliar neutral cage.","date":"1992","source":"Neuropharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/1356251","citation_count":24,"is_preprint":false},{"pmid":"9554804","id":"PMC_9554804","title":"Comparative effects of glibenclamide, tedisamil, dofetilide, E-4031, and BRL-32872 on protein kinase A-activated chloride current in guinea pig ventricular myocytes.","date":"1998","source":"Journal of cardiovascular pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/9554804","citation_count":24,"is_preprint":false},{"pmid":"7980451","id":"PMC_7980451","title":"Kinetic and physical studies of beta-lactamase inhibition by a novel penem, BRL 42715.","date":"1994","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/7980451","citation_count":24,"is_preprint":false},{"pmid":"32003020","id":"PMC_32003020","title":"α2A -AR antagonism by BRL-44408 maleate attenuates acute lung injury in rats with downregulation of ERK1/2, p38MAPK, and p65 pathway.","date":"2020","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/32003020","citation_count":23,"is_preprint":false},{"pmid":"2841863","id":"PMC_2841863","title":"Effect of a thermogenic agent, BRL 26830A, on insulin receptors in obese mice.","date":"1988","source":"The American journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/2841863","citation_count":23,"is_preprint":false},{"pmid":"2166921","id":"PMC_2166921","title":"Behavioural effects in gerbils of the 5-HT3 receptor antagonists, BRL 43694 and ICS 205-930, under circumstances of high and low light intensity.","date":"1990","source":"Neuropharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/2166921","citation_count":23,"is_preprint":false},{"pmid":"1688048","id":"PMC_1688048","title":"Effects of a beta 3-adrenoceptor agonist, BRL 26830A, on insulin and glucagon release in mice.","date":"1991","source":"Endocrinologia japonica","url":"https://pubmed.ncbi.nlm.nih.gov/1688048","citation_count":23,"is_preprint":false},{"pmid":"1324062","id":"PMC_1324062","title":"Comparative effects of BRL 38227, nitrendipine and isoprenaline on carbachol- and histamine-stimulated phosphoinositide metabolism in airway smooth muscle.","date":"1992","source":"British journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/1324062","citation_count":22,"is_preprint":false},{"pmid":"30538798","id":"PMC_30538798","title":"Ethyl Acetate Fraction of Hemerocallis citrina Baroni Decreases Tert-butyl Hydroperoxide-Induced Oxidative Stress Damage in BRL-3A Cells.","date":"2018","source":"Oxidative medicine and cellular longevity","url":"https://pubmed.ncbi.nlm.nih.gov/30538798","citation_count":22,"is_preprint":false},{"pmid":"31152848","id":"PMC_31152848","title":"Study on the metabolism toxicity, susceptibility and mechanism of di-(2-ethylhexyl) phthalate on rat liver BRL cells with insulin resistance in vitro.","date":"2019","source":"Toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/31152848","citation_count":21,"is_preprint":false},{"pmid":"27837920","id":"PMC_27837920","title":"The Schizophrenia-Associated BRD1 Gene Regulates Behavior, Neurotransmission, and Expression of Schizophrenia Risk Enriched Gene Sets in Mice.","date":"2016","source":"Biological psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/27837920","citation_count":20,"is_preprint":false},{"pmid":"29125642","id":"PMC_29125642","title":"Genistein Ameliorates Fat Accumulation Through AMPK Activation in Fatty Acid-Induced BRL Cells.","date":"2017","source":"Journal of food science","url":"https://pubmed.ncbi.nlm.nih.gov/29125642","citation_count":20,"is_preprint":false},{"pmid":"39565874","id":"PMC_39565874","title":"NIT2 dampens BRD1 phase separation and restrains oxidative phosphorylation to enhance chemosensitivity in gastric cancer.","date":"2024","source":"Science translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/39565874","citation_count":19,"is_preprint":false},{"pmid":"27256846","id":"PMC_27256846","title":"The BRPF2/BRD1-MOZ complex is involved in retinoic acid-induced differentiation of embryonic stem cells.","date":"2016","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/27256846","citation_count":19,"is_preprint":false},{"pmid":"22341945","id":"PMC_22341945","title":"The Schizophrenia and Bipolar Disorder associated BRD1 gene is regulated upon chronic restraint stress.","date":"2012","source":"European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/22341945","citation_count":19,"is_preprint":false},{"pmid":"30590179","id":"PMC_30590179","title":"Brain proteome changes in female Brd1+/- mice unmask dendritic spine pathology and show enrichment for schizophrenia risk.","date":"2018","source":"Neurobiology of disease","url":"https://pubmed.ncbi.nlm.nih.gov/30590179","citation_count":19,"is_preprint":false},{"pmid":"10602503","id":"PMC_10602503","title":"The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene.","date":"1999","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/10602503","citation_count":19,"is_preprint":false},{"pmid":"34194602","id":"PMC_34194602","title":"Total Flavonoids of Crocus sativus Petals Release tert-Butyl Hydroperoxide-Induced Oxidative Stress in BRL-3A Cells.","date":"2021","source":"Oxidative medicine and cellular longevity","url":"https://pubmed.ncbi.nlm.nih.gov/34194602","citation_count":19,"is_preprint":false},{"pmid":"11192182","id":"PMC_11192182","title":"Development of bovine embryos on Vero/BRL cell monolayers (mixed co-culture).","date":"2000","source":"Theriogenology","url":"https://pubmed.ncbi.nlm.nih.gov/11192182","citation_count":19,"is_preprint":false},{"pmid":"29102763","id":"PMC_29102763","title":"A reactive oxygen species activation mechanism contributes to Sophoridine-induced apoptosis in rat liver BRL-3A cells.","date":"2018","source":"Journal of ethnopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/29102763","citation_count":19,"is_preprint":false},{"pmid":"33556623","id":"PMC_33556623","title":"Crystal structure of the BRPF2 PWWP domain in complex with DNA reveals a different binding mode than the HDGF family of PWWP domains.","date":"2021","source":"Biochimica et biophysica acta. Gene regulatory mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/33556623","citation_count":18,"is_preprint":false},{"pmid":"28845526","id":"PMC_28845526","title":"Serine peptidase inhibitor Kazal type I (SPINK1) promotes BRL-3A cell proliferation via p38, ERK, and JNK pathways.","date":"2017","source":"Cell biochemistry and function","url":"https://pubmed.ncbi.nlm.nih.gov/28845526","citation_count":18,"is_preprint":false},{"pmid":"25752290","id":"PMC_25752290","title":"Interleukin 18 augments growth ability via NF-κB and p38/ATF2 pathways by targeting cyclin B1, cyclin B2, cyclin A2, and Bcl-2 in BRL-3A rat liver cells.","date":"2015","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/25752290","citation_count":18,"is_preprint":false},{"pmid":"2161551","id":"PMC_2161551","title":"Chronic administration of the 5-HT3 receptor antagonist BRL 43694; effects on reflex epilepsy and social behaviour of the Mongolian gerbil.","date":"1990","source":"Psychopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/2161551","citation_count":18,"is_preprint":false},{"pmid":"30405140","id":"PMC_30405140","title":"Brain volumetric alterations accompanied with loss of striatal medium-sized spiny neurons and cortical parvalbumin expressing interneurons in Brd1+/- mice.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/30405140","citation_count":17,"is_preprint":false},{"pmid":"31264285","id":"PMC_31264285","title":"Effect of oleic acid on induction of steatosis and cytotoxicity in BRL 3A cells.","date":"2019","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31264285","citation_count":17,"is_preprint":false},{"pmid":"33912056","id":"PMC_33912056","title":"P- Hydroxybenzyl Alcohol Alleviates Oxidative Stress in a Nonalcoholic Fatty Liver Disease Larval Zebrafish Model and a BRL-3A Hepatocyte Via the Nrf2 Pathway.","date":"2021","source":"Frontiers in pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/33912056","citation_count":17,"is_preprint":false},{"pmid":"8095215","id":"PMC_8095215","title":"Evidence that famciclovir (BRL 42810) and its associated metabolites do not inhibit the 6 beta-hydroxylation of testosterone in human liver microsomes.","date":"1993","source":"Drug metabolism and disposition: the biological fate of chemicals","url":"https://pubmed.ncbi.nlm.nih.gov/8095215","citation_count":17,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":55674,"output_tokens":3239,"usd":0.107803,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10670,"output_tokens":4244,"usd":0.079725,"stage2_stop_reason":"end_turn"},"total_usd":0.187528,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"BRD1 (BRPF2) forms a novel histone acetyltransferase complex with HBO1 and bridges HBO1 to its activator ING4; this Hbo1-Brd1 complex is responsible for global acetylation of histone H3 at lysine 14 (H3K14ac) in erythroblasts, and Brd1-deficient embryos show profoundly decreased H3K14 acetylation and impaired fetal liver erythropoiesis.\",\n      \"method\": \"Biochemical co-immunoprecipitation, genome-wide ChIP mapping in erythroblasts, conditional knockout mouse model with phenotypic rescue by Gata1 forced expression\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, genome-wide ChIP, KO mouse with specific phenotypic readout and partial rescue experiment across multiple orthogonal methods in one study\",\n      \"pmids\": [\"21753189\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Brd1 localizes at Cd8 gene enhancers in thymocytes as part of the Hbo1 HAT complex and is required for H3K14 acetylation at these enhancers; deletion of Brd1 in haematopoietic progenitors causes variegated Cd8 expression, demonstrating that Brd1-mediated H3K14ac is an epigenetic mark that promotes transcription machinery recruitment to Cd8 enhancers.\",\n      \"method\": \"Conditional knockout mouse model, ChIP analysis of Brd1 occupancy and H3K14ac at Cd8 enhancers, co-immunoprecipitation of Brd1-Hbo1 complex in thymocytes\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, locus-specific ChIP, and conditional KO with defined cellular phenotype, all in one study\",\n      \"pmids\": [\"25519988\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"A short N-terminal region of BRPF2 (BRD1) is sufficient to bind the HBO1 MYST domain and potentiate its HAT activity toward H3K14 on free histone H3, H4, and nucleosomal H3; the crystal structure of the HBO1 MYST domain in complex with this BRPF2 segment identified key interface residues responsible for the interaction.\",\n      \"method\": \"Crystal structure of HBO1-BRPF2 complex, in vitro HAT activity assays with truncation mutants, mutagenesis of interface residues, cell biological validation\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus in vitro reconstitution HAT assay plus mutagenesis plus cell biology in a single rigorous study\",\n      \"pmids\": [\"28334966\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The second PHD finger (PHD2) within the PZPM motif of human BRPF2 (BRD1) adopts an atypical two-strand β-sheet structure distinct from canonical PHD fingers, and this domain can bind DNA non-specifically via an evolutionarily conserved positively charged surface.\",\n      \"method\": \"NMR solution structure determination, in vitro DNA-binding assays\",\n      \"journal\": \"Journal of structural biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — NMR structure with binding assay but single lab, no mutagenesis validation of binding surface\",\n      \"pmids\": [\"22820306\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"The BRPF2 (BRD1) PWWP domain binds double-stranded DNA without sequence selectivity, and its crystal structure in complex with a 12-mer dsDNA reveals that the domain interacts with the major groove of DNA—a binding mode distinct from the minor-groove engagement observed in the HDGF family of PWWP domains.\",\n      \"method\": \"Crystal structure of BRPF2 PWWP domain in complex with dsDNA, family-wide dsDNA binding assays\",\n      \"journal\": \"Biochimica et biophysica acta. Gene regulatory mechanisms\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure with binding assay validation; single lab but orthogonal structural and biochemical methods\",\n      \"pmids\": [\"33556623\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"BRD1 interacts with chromatin remodeling proteins (e.g., PBRM1) and histone modifiers (e.g., MYST2/HBO1, SUV420H1) as identified by Co-IP/mass spectrometry; BRD1 isoforms (BRD1-S and BRD1-L) show isoform-specific protein interactions and primarily bind near transcription start sites to regulate expression of numerous genes including those involved in brain development.\",\n      \"method\": \"Co-immunoprecipitation followed by mass spectrometry, ChIP-seq in stable human cell lines expressing epitope-tagged BRD1-S and BRD1-L, microarray gene expression profiling\",\n      \"journal\": \"Genome medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP/MS interactome plus ChIP-seq, single lab but two orthogonal methods with functional expression data\",\n      \"pmids\": [\"27142060\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Heterozygous deletion of Brd1 in mice causes cerebral histone H3K14 hypoacetylation, striatal dopamine/serotonin abnormalities, cortical excitation-inhibition imbalance with loss of parvalbumin interneurons, and schizophrenia-relevant behavioral phenotypes; RNA-sequencing revealed differential expression of schizophrenia GWAS risk genes including Cacna1c, Drd2, and Tcf4.\",\n      \"method\": \"Brd1+/- mouse model, behavioral testing, electrophysiology, RNA-sequencing of cortical and striatal micropunches, immunohistochemistry for parvalbumin, histone modification analysis\",\n      \"journal\": \"Biological psychiatry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined KO with multiple orthogonal readouts (behavior, electrophysiology, transcriptomics, histone marks), single lab\",\n      \"pmids\": [\"27837920\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"BRPF2 (BRD1) depletion in mouse embryonic stem cells reduces global H3K14 acetylation and impairs retinoic acid-induced differentiation; co-immunoprecipitation in differentiated ESCs revealed a physical interaction between BRPF2 and the HAT MOZ, suggesting BRPF2-MOZ complexes regulate ESC differentiation via H3K14ac.\",\n      \"method\": \"siRNA knockdown of BRPF2 in ESCs, alkaline phosphatase activity assay, co-immunoprecipitation, western blot for H3K14ac\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP plus KD phenotype across multiple orthogonal readouts, single lab\",\n      \"pmids\": [\"27256846\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"BRD1 protein is localized to the nucleus, perikaryal cytosol, and proximal dendrites of neurons in adult rat, rabbit, and human CNS as detected by immunohistochemistry; quantitative mRNA analysis in developing fetal pig brain showed high early embryonic expression with intense nuclear staining of neuroepithelial cells, shifting to less nuclear staining in more mature neurons.\",\n      \"method\": \"Immunohistochemistry on adult CNS sections, quantitative mRNA analysis in developing fetal pig brain\",\n      \"journal\": \"Molecular psychiatry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization by IHC, single lab, no direct functional consequence linked to the localization\",\n      \"pmids\": [\"16924267\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"The BRD1 (BRL) gene encodes a nuclear protein of ~120 kDa that contains a bromodomain, a cysteine-rich region related to the AF10/AF17 leukaemia proteins, four LXXLL motifs, and predicted nuclear localization signals; a monoclonal antibody confirmed nuclear localization within spermatocytes and widespread expression.\",\n      \"method\": \"cDNA cloning, protein sequence analysis, monoclonal antibody immunostaining, expression analysis by Northern/Western blot\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — initial cloning and localization study, single lab, no functional mechanistic follow-up\",\n      \"pmids\": [\"10602503\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"NIT2 interacts with BRD1 to inhibit HBO1-mediated H3K14 acetylation; upon 5-FU stimulation, Src phosphorylates NIT2 at Y49, promoting NIT2 dissociation from BRD1 and its autophagic degradation, which causes BRD1 to form phase-separated condensates and bind histone H3, increasing H3K14ac and RELA-dependent OXPHOS gene expression, thereby driving 5-FU chemoresistance in gastric cancer.\",\n      \"method\": \"CRISPR-Cas9 screen, Co-IP, proximity ligation assay, patient-derived organoids, xenograft tumors, biochemical fractionation, phase separation assays, Src kinase assay\",\n      \"journal\": \"Science translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods including Co-IP, kinase assay, and phase separation assays in one study, single lab\",\n      \"pmids\": [\"39565874\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Benzoisoquinolinedione compounds (including BAY-299) selectively inhibit the bromodomain of BRPF2 (BRD1) with IC50 of 67 nM, and cellular activity was confirmed using a BRPF2-histone H3.3/H4 interaction assay, demonstrating that the BRPF2 bromodomain functions as a reader of acetylated lysine marks on histones.\",\n      \"method\": \"High-throughput biochemical screening, SAR-guided medicinal chemistry, selectivity profiling across bromodomains, cellular BRPF2-histone interaction assay\",\n      \"journal\": \"Journal of medicinal chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical inhibitor assay with cellular validation, multiple selectivity controls, single lab\",\n      \"pmids\": [\"28402630\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"BRD1 (BRPF2) is a scaffold/regulatory subunit of HBO1 (MYST2) histone acetyltransferase complexes, where its N-terminal region directly contacts the HBO1 MYST domain (crystal structure solved) to potentiate H3K14 acetylation on nucleosomes; BRD1 bridges HBO1 to the activator ING4, and the complex is the major H3K14 HAT required for transcriptional activation of developmental regulator genes in erythropoiesis, T-cell development, and ESC differentiation, while BRD1's bromodomain acts as an acetyl-lysine reader and its PWWP and PHD domains mediate non-sequence-specific DNA binding; loss of Brd1 causes brain-relevant H3K14 hypoacetylation and schizophrenia-related behavioral and neurochemical phenotypes in mice.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"BRD1 (BRPF2) is a scaffolding and regulatory subunit of MYST-family histone acetyltransferase complexes that delivers histone H3 lysine 14 acetylation (H3K14ac) at developmental gene loci, coupling chromatin modification to transcriptional activation across erythropoiesis, T-cell development, and embryonic stem cell differentiation [#0, #1, #7]. A short N-terminal segment of BRD1 directly engages the HBO1 (MYST2) MYST domain to potentiate its acetyltransferase activity toward free and nucleosomal H3, an interaction defined at residue resolution by the HBO1–BRPF2 crystal structure [#2]; within the complex BRD1 also bridges HBO1 to the activator ING4 and is the major activity responsible for global H3K14ac in erythroblasts, where its loss impairs fetal liver erythropoiesis [#0]. BRD1 likewise interacts with the related HAT MOZ to control H3K14ac-dependent ESC differentiation [#7], and recruits to gene enhancers and transcription start sites to drive expression of lineage regulators [#1, #5]. Chromatin engagement is mediated by multiple reader/binding modules: a bromodomain that reads acetyl-lysine marks on histone H3.3/H4 [#11], and PWWP and atypical PHD domains that bind double-stranded DNA non-specifically, the PWWP domain engaging the DNA major groove [#3, #4]. BRD1 activity is restrained by NIT2, whose Src-dependent phosphorylation and degradation releases BRD1 to form phase-separated condensates that bind histone H3 and elevate H3K14ac, linking the complex to RELA-dependent transcription and chemoresistance [#10]. Heterozygous loss of Brd1 in mice causes cerebral H3K14 hypoacetylation and schizophrenia-relevant behavioral, neurochemical, and cortical interneuron phenotypes, with dysregulation of schizophrenia risk genes [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"The founding question was what BRD1 encodes; cloning established it as a nuclear bromodomain-containing protein with a cysteine-rich region and LXXLL motifs, framing it as a chromatin-associated factor.\",\n      \"evidence\": \"cDNA cloning, protein sequence analysis, and antibody immunostaining showing nuclear localization\",\n      \"pmids\": [\"10602503\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Initial characterization with no functional or enzymatic assignment\", \"No identified protein partners or chromatin targets\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Tissue-level expression mapping addressed where BRD1 acts, placing the protein in neuronal nuclei and CNS development before any molecular function was known.\",\n      \"evidence\": \"Immunohistochemistry across mammalian CNS and mRNA quantification in developing fetal pig brain\",\n      \"pmids\": [\"16924267\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Localization not linked to a molecular activity\", \"No mechanistic consequence of CNS expression defined\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"The defining mechanistic question — what enzymatic complex BRD1 belongs to — was answered by showing it bridges HBO1 to ING4 and is required for global H3K14 acetylation in vivo, establishing BRD1 as a HAT-complex subunit controlling erythropoiesis.\",\n      \"evidence\": \"Reciprocal Co-IP, genome-wide ChIP in erythroblasts, and conditional knockout mouse with Gata1 rescue\",\n      \"pmids\": [\"21753189\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the HBO1 interaction not yet defined\", \"Direct contribution of BRD1 domains to substrate selectivity unresolved\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"How BRD1 contacts chromatin DNA was probed by structure determination of its PHD2 domain, revealing an atypical fold that binds DNA non-specifically via a conserved basic surface.\",\n      \"evidence\": \"NMR solution structure and in vitro DNA-binding assays\",\n      \"pmids\": [\"22820306\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No mutagenesis validation of the binding surface\", \"Functional role of DNA binding in cells untested\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether BRD1-mediated H3K14ac functions as an activating mark at specific loci was established by showing BRD1 occupies Cd8 enhancers and is required for stable Cd8 expression in T-cell development.\",\n      \"evidence\": \"Conditional KO mouse, locus-specific ChIP for occupancy and H3K14ac, and Co-IP of the Brd1-Hbo1 complex in thymocytes\",\n      \"pmids\": [\"25519988\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking H3K14ac to transcription machinery recruitment not directly demonstrated\", \"Generalizability beyond Cd8 enhancers not established here\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The interactome and genomic targeting of BRD1 were broadened, identifying isoform-specific partners (PBRM1, MYST2, SUV420H1) and TSS-proximal binding regulating brain-development genes.\",\n      \"evidence\": \"Co-IP/mass spectrometry interactome plus ChIP-seq and expression profiling of tagged BRD1-S and BRD1-L isoforms\",\n      \"pmids\": [\"27142060\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus indirect nature of some interactions not resolved\", \"Functional consequences of isoform-specific interactions not dissected\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"BRD1's role in pluripotency was addressed by showing its depletion lowers H3K14ac and blocks RA-induced ESC differentiation, and that it partners not only with HBO1 but also with MOZ.\",\n      \"evidence\": \"siRNA knockdown in ESCs, differentiation assay, Co-IP, and H3K14ac western blot\",\n      \"pmids\": [\"27256846\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single Co-IP for the MOZ interaction without reciprocal validation\", \"Whether MOZ and HBO1 complexes are functionally distinct in ESCs unresolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The neurological relevance of BRD1 was tested in vivo, linking heterozygous loss to H3K14 hypoacetylation, cortical interneuron and neurochemical deficits, and dysregulation of schizophrenia risk genes.\",\n      \"evidence\": \"Brd1+/- mouse with behavior, electrophysiology, immunohistochemistry, histone marks, and RNA-seq of brain micropunches\",\n      \"pmids\": [\"27837920\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal chain from H3K14 hypoacetylation to behavior not directly demonstrated\", \"No human genetic causation established within this study\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The structural and biochemical basis of HBO1 activation was resolved by crystallizing the HBO1 MYST domain with a minimal BRPF2 segment and showing this segment is sufficient to potentiate H3K14 HAT activity.\",\n      \"evidence\": \"Crystal structure, in vitro HAT assays with truncation and interface mutants, and cell validation\",\n      \"pmids\": [\"28334966\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure limited to the BRPF2 N-terminal segment, not full-length BRD1\", \"Role of BRD1 reader domains in the assembled complex not captured\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The function of the BRD1 bromodomain as an acetyl-lysine reader was confirmed pharmacologically, with selective inhibitors blocking BRPF2 binding to acetylated H3.3/H4.\",\n      \"evidence\": \"Biochemical inhibitor screening, SAR, bromodomain selectivity profiling, and cellular BRPF2-histone interaction assay\",\n      \"pmids\": [\"28402630\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological acetyl-lysine targets read by the bromodomain not mapped\", \"Cellular phenotype of bromodomain inhibition not characterized here\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"How the BRD1 PWWP domain engages chromatin DNA was clarified structurally, showing major-groove dsDNA binding distinct from HDGF-family PWWP domains.\",\n      \"evidence\": \"Crystal structure of the PWWP domain bound to dsDNA and family-wide binding assays\",\n      \"pmids\": [\"33556623\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo contribution of PWWP DNA binding to BRD1 targeting untested\", \"Coordination with PHD and bromodomain in chromatin engagement unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"A regulatory switch controlling BRD1 activity was uncovered: NIT2 normally inhibits HBO1-mediated H3K14ac through BRD1, and Src-driven NIT2 degradation releases BRD1 to form condensates that boost H3K14ac and RELA-dependent transcription, driving chemoresistance.\",\n      \"evidence\": \"CRISPR screen, Co-IP, proximity ligation, kinase assay, phase-separation assays, organoids, and xenografts\",\n      \"pmids\": [\"39565874\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological relevance of BRD1 phase separation beyond chemoresistance unresolved\", \"Single-lab study without independent replication of the condensate model\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How BRD1's multiple chromatin-reading modules (bromodomain, PWWP, PHD) are integrated for genome-wide targeting, and whether HBO1- versus MOZ-containing complexes have distinct in vivo functions, remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No full-length BRD1 structure within an assembled HAT complex\", \"Division of labor between HBO1 and MOZ complexes not resolved\", \"Rules governing locus-specific recruitment not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [2, 11]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [3, 4]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [8, 9]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [1, 0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 5]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [0, 7]}\n    ],\n    \"complexes\": [\n      \"HBO1 (MYST2) histone acetyltransferase complex\",\n      \"MOZ histone acetyltransferase complex\"\n    ],\n    \"partners\": [\n      \"HBO1\",\n      \"MYST2\",\n      \"ING4\",\n      \"MOZ\",\n      \"PBRM1\",\n      \"SUV420H1\",\n      \"NIT2\",\n      \"RELA\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}