Affinage

BRPF1

Peregrin · UniProt P55201

Length
1214 aa
Mass
137.5 kDa
Annotated
2026-06-09
62 papers in source corpus 31 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BRPF1 is a multivalent chromatin scaffold that assembles and activates MYST-family histone acetyltransferase complexes — together with MOZ (KAT6A), MORF (KAT6B), and HBO1 (KAT7) plus ING5 and MEAF6 — to deposit acetylation and propionylation at histone H3K23 and to read and bridge other histone marks during development (PMID:26626149, PMID:27500495, PMID:32010779). It engages chromatin through three reader modules: a PWWP domain that binds H3K36me3 (PMID:20400950), a PZP (PHD–zinc-knuckle–PHD) domain that bivalently contacts the H3 tail and extranucleosomal DNA — with DNA binding dominating — to drive nucleosome unwrapping and enable HAT complex recruitment and nucleosomal acetylation (PMID:26626149, PMID:31711755), and a bromodomain that selectively recognizes acetyllysines including H2AK5ac, H4K12ac, and H3K14ac and reads di-acetylated H4 marks such as H4K5acK8ac (PMID:24333487, PMID:25281266, PMID:33554132). Through this scaffold activity BRPF1 functions both as a transcriptional activator and silencer, and in human embryonic stem cells it bridges H3K4me3 and H3K23ac to keep stemness gene chromatin open, with its N-terminal and PZP modules being essential and the PWWP domain only partially required (PMID:36711238). In vivo, Brpf1 is required for H3K23 acetylation/propionylation and for normal forebrain neurogenesis, neuronal migration, dendritic and synaptic development, hematopoietic stem cell maintenance, and embryonic vascular and neural-tube development, where its loss deregulates Hox and multipotency gene programs (PMID:25757017, PMID:25773539, PMID:27500495, PMID:32010779, PMID:31213987). Monoallelic pathogenic BRPF1 variants impair H3K23 acetylation and propionylation and cause a syndromic intellectual disability disorder in humans (PMID:27939640, PMID:27939639, PMID:32010779). BRPF1 is also co-opted in cancer, where it directs MOZ/MORF-mediated H3K14 acetylation and chromatin opening at oncogenic loci and partners with ERα and NUP98-fusion oncoproteins to sustain tumor cell programs [PMID:34285329, PMID:39113071, PMID:bio_10.1101_2024.12.02.624182].

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1994 Medium

    Established BRPF1 (BR140) as a nuclear zinc-finger protein with homology to the TFIID subunit TAF250, providing the first hint of a transcription-associated chromatin role.

    Evidence cDNA cloning, sequence analysis, and immunolocalization of the BR140 protein

    PMID:7906940

    Open questions at the time
    • No enzymatic or binding mechanism established
    • Functional role in transcription not demonstrated
  2. 2009 High

    Genetic loss-of-function in two vertebrates placed BRPF1 within the MOZ HAT complex controlling Hox/Zic patterning, connecting the protein to developmental gene regulation.

    Evidence Medaka forward-genetic brpf1 mutant and parallel mouse MOZ knockout with in situ hybridization

    PMID:19254709

    Open questions at the time
    • Molecular mechanism of complex assembly not resolved
    • Direct chromatin targets not mapped
  3. 2010 High

    Answered how BRPF1 reads methylated chromatin by defining the PWWP domain as an H3K36me3 reader at atomic resolution.

    Evidence X-ray crystal structure of the PWWP–H3K36me3 peptide complex with binding validation

    PMID:20400950

    Open questions at the time
    • Contribution of PWWP reading to complex recruitment in vivo not quantified
    • Other reader modules unaddressed
  4. 2013 High

    Defined the BRPF1 bromodomain as a histone acetyllysine reader and mapped the acetyllysine-coordinating residues, identifying a second chromatin-engagement module.

    Evidence NMR chemical shift perturbation, molecular dynamics, and bromodomain ligand-binding assays

    PMID:24333487

    Open questions at the time
    • In vivo relevance of each acetyl mark not established
    • Bromodomain contribution to HAT recruitment not tested
  5. 2014 High

    Provided atomic-resolution structures of the bromodomain bound to H2AK5ac and H4K12ac, establishing the molecular basis of acetyllysine recognition including ordered waters.

    Evidence X-ray crystallography of bromodomain–peptide complexes with binding-pocket mutagenesis

    PMID:25281266

    Open questions at the time
    • Multivalent or di-acetyl recognition not yet characterized
    • Functional output of binding not measured
  6. 2015 High

    Resolved how BRPF1 engages whole nucleosomes by showing the PZP domain bivalently contacts H3 and DNA to promote nucleosome unwrapping and enable HAT complex recruitment and nucleosomal acetylation.

    Evidence Biochemical reconstitution, FRET nucleosome dynamics, and HAT activity assays on the MOZ-BRPF1-ING5-hEaf6 complex

    PMID:26626149

    Open questions at the time
    • Relative contributions of H3-tail vs DNA binding not yet dissected
    • Structural detail of PZP–H3 contact pending
  7. 2015 High

    Demonstrated that BRPF1 is required in vivo for forebrain neurogenesis, embryonic viability, and progenitor proliferation, acting as both activator and silencer of developmental genes.

    Evidence Conditional and constitutive Brpf1 mouse knockouts with histology, BrdU cell-cycle analysis, and transcriptome profiling

    PMID:25568313 PMID:25757017 PMID:25773539

    Open questions at the time
    • Direct chromatin targets versus indirect effects not distinguished
    • Mechanistic link from HAT activity to specific gene programs incomplete
  8. 2016 High

    Linked BRPF1 to a specific epigenetic mark and stem-cell function by showing it is required for H3K23ac and multipotency gene expression in hematopoietic stem cells.

    Evidence Hematopoietic-specific Brpf1 knockout with flow cytometry, H3K23ac immunoblotting, ROS/apoptosis assays, and expression profiling

    PMID:27500495

    Open questions at the time
    • Whether H3K23ac loss is causal for each phenotype not isolated
    • Direct genomic sites of H3K23ac deposition not mapped
  9. 2016 High

    Established BRPF1 as a human disease gene by showing monoallelic variants impair its acetyltransferase co-activation and H3K23ac, causing an intellectual disability syndrome.

    Evidence Patient variant functional assays, H3K23ac immunoblotting in patient fibroblasts and Brpf1-KO mice, and localization studies

    PMID:27939639 PMID:27939640

    Open questions at the time
    • Genotype–phenotype correlations across variants not fully resolved
    • Tissue-specific consequences of haploinsufficiency incompletely defined
  10. 2019 High

    Refined the nucleosome-engagement mechanism by showing extranucleosomal DNA binding dominates over H3-tail binding in the PZP domain and that both are required for tight nucleosome binding and HAT function.

    Evidence X-ray crystallography of the PZP–H3 complex, ITC, and HAT activity assays on the BRPF1-MORF-ING5-MEAF6 complex

    PMID:31711755

    Open questions at the time
    • In vivo importance of DNA versus H3 binding not tested
    • Coordination with PWWP and bromodomain on the same nucleosome unresolved
  11. 2019 High

    Connected Brpf1 dosage to neuronal circuit function by showing haploinsufficiency reduces dendritic complexity, spine density, and excitatory transmission, impairing learning and memory.

    Evidence Conditional Brpf1 heterozygous mice with morphology, patch-clamp electrophysiology, and behavioral assays

    PMID:31213987

    Open questions at the time
    • Molecular targets driving synaptic deficits not defined
    • Cell-autonomous versus circuit-level contributions unclear
  12. 2020 High

    Expanded the catalytic output of BRPF1 complexes by showing they deposit H3K23 propionylation as well as acetylation, both abolished by Brpf1 loss and impaired by patient variants.

    Evidence In vitro acylation assays, mass spectrometry, ATAC-See in mouse embryos/fibroblasts, and patient variant assays

    PMID:32010779

    Open questions at the time
    • Functional distinction between acetylation and propionylation not resolved
    • Genomic distribution of H3K23pr not mapped
  13. 2020 High

    Extended bromodomain reading specificity to di-acetylated H4 and identified the non-canonical pocket regions mediating recognition of the second acetyl mark.

    Evidence ITC, NMR chemical shift perturbation, analytical ultracentrifugation, and mutagenesis

    PMID:33554132

    Open questions at the time
    • In vivo role of di-acetyl reading not tested
    • Integration with other reader modules unaddressed
  14. 2020 Medium

    Revealed isoform-specific BRPF1 functions in hematopoietic progenitors, with one isoform promoting expansion and another quiescence via chromatin accessibility and the Mn1 self-renewal gene.

    Evidence Bromodomain inhibitor screen, isoform-specific overexpression/knockdown, ATAC-seq, and Mn1 epistasis in HSPCs

    PMID:31565729

    Open questions at the time
    • Single-lab study without independent replication
    • Molecular basis of isoform divergence unclear
  15. 2023 Medium

    Defined BRPF1 as a chromatin bridge in human pluripotency by showing it links H3K4me3 and H3K23ac to keep stemness gene chromatin open, with N-terminal/PZP modules essential and PWWP partially dispensable.

    Evidence BRPF1 KO in hESCs with CUT&RUN/ChIP, ATAC-seq, and domain-deletion rescue assays

    PMID:36711238

    Open questions at the time
    • Single-lab study
    • Mechanism by which marks are physically bridged not structurally resolved
  16. 2023 Medium

    Mapped a non-histone bromodomain interactome and validated ILF3 as a partner, expanding BRPF1 function beyond histone reading.

    Evidence Unnatural amino acid photo-crosslinking proteomics with ITC and co-IP validation

    PMID:38072045

    Open questions at the time
    • Functional consequence of ILF3 binding not established
    • Single Co-IP/ITC validation for one partner
  17. 2025 Medium

    Identified an upstream regulator of BRPF1 expression, showing FBRSL1 with YY1 controls BRPF1 transcription and that FBRSL1 truncations downregulate BRPF1 in patients.

    Evidence ChIP-seq of FBRSL1–YY1 at the BRPF1 promoter, qRT-PCR in patient cells, and Xenopus loss-of-function

    PMID:40658195

    Open questions at the time
    • Single-lab study
    • Direct versus indirect regulation of BRPF1 not fully separated
  18. 2025 Medium

    Documented oncogenic and drug-resistance roles for BRPF1 across cancers, where it directs HAT-mediated chromatin opening at oncogenic and resistance loci and partners with ERα and NUP98 fusions.

    Evidence ChIP-seq/CUT&RUN occupancy, ATAC-seq, genetic and pharmacological inhibition, and xenograft/organoid models across HCC, breast, prostate, AML, and TNBC

    PMID:31851932 PMID:34285329 PMID:36357379 PMID:39113071 PMID:40583060

    Open questions at the time
    • Mostly single-lab studies per tumor type
    • Direct versus complex-mediated chromatin targeting not always distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the three reader modules (PWWP, PZP, bromodomain) are coordinated on a single nucleosome to integrate H3K36me3, DNA, and acetyl marks into productive HAT recruitment, and how this generates locus-specific gene activation versus silencing, remains unresolved.
  • No integrated structural model of full-length BRPF1 on a nucleosome
  • Genome-wide map of H3K23ac/H3K23pr deposition incomplete
  • Rules distinguishing activator from silencer function unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 6 GO:0003677 DNA binding 5 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ESR1ILF3ING5KAT6AKAT6BKAT7MEAF6USP35
Complex memberships
BRPF1-MORF-ING5-MEAF6 HAT complexHBO1/KAT7 complexMOZ-BRPF1-ING5-hEaf6 HAT complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 The PWWP domain of BRPF1 directly binds H3K36me3; the crystal structure of the PWWP domain in complex with an H3K36me3-derived peptide was determined, establishing this domain as a trimethyl-lysine reader. X-ray crystallography (structure of PWWP–H3K36me3 peptide complex) Nature structural & molecular biology High 20400950
2013 The BRPF1 bromodomain preferentially recognizes acetylated lysines H2AK5ac, H4K12ac, and H3K14ac on histone N-terminal tails; key residues coordinating acetyllysine were mapped by NMR chemical shift perturbation and molecular dynamics simulations. NMR titration/chemical shift perturbation, molecular dynamics simulations, bromodomain ligand-binding assays Journal of molecular biology High 24333487
2014 X-ray crystal structures of the BRPF1 bromodomain in complex with H2AK5ac and H4K12ac histone peptides were solved; site-directed mutagenesis of binding-pocket residues confirmed their roles in ligand coordination, and ordered water molecules were identified as essential components of ligand recognition. X-ray crystallography, site-directed mutagenesis, binding assays FEBS letters High 25281266
2015 The PZP domain (PHD-zinc-knuckle-PHD) of BRPF1 forms a 2:1 stoichiometry complex with the nucleosome, bivalently contacting histone H3 and DNA. This interaction shifts the DNA unwrapping/rewrapping equilibrium toward the unwrapped state and is required for MOZ-BRPF1-ING5-hEaf6 HAT complex recruitment to chromatin and acetylation of nucleosomal histones. Biochemical reconstitution, FRET-based nucleosome dynamics assay, HAT activity assays on nucleosomal substrates, structural characterization Nucleic acids research High 26626149
2015 Forebrain-specific deletion of mouse Brpf1 causes early postnatal lethality, neocortical abnormalities, and partial callosal agenesis; the mutant forebrain has fewer Tbr2+ intermediate neuronal progenitors and altered expression of Robo3, Otx1, and multiple Hox genes, indicating Brpf1 acts as both an activator and silencer of gene expression in vivo. Conditional Brpf1 knockout (Cre-lox), immunohistochemistry, transcriptome analysis The Journal of biological chemistry High 25568313
2015 Forebrain-specific Brpf1 deletion causes dentate gyrus hypoplasia traceable to compromised Sox2+ neural stem cells and Tbr2+ intermediate neuronal progenitors, with deregulated neuronal migration, cell cycle progression, and transcriptional control. Conditional Brpf1 knockout (Cre-lox), immunohistochemistry, BrdU cell cycle analysis, gene expression profiling PLoS genetics High 25757017
2015 Whole-body Brpf1 deletion in mouse causes embryonic lethality at ~E9.5 with vascular defects in placenta and yolk sac, abnormal neural tube closure, and inhibition of embryonic fibroblast and hematopoietic progenitor proliferation; molecular analysis showed reduced Rpl10-like gene and p27, and increased p16 and a Scp3-homolog. Constitutive Brpf1 knockout, embryo phenotyping, cell proliferation assays, gene expression analysis The Journal of biological chemistry High 25773539
2016 Hematopoietic-specific Brpf1 deletion in mice causes acute bone marrow failure, aplastic anemia, and early lethality; mutant bone marrow and fetal liver show severe HSC and progenitor deficiency with elevated reactive oxygen species, senescence, and apoptosis. BRPF1 is required for H3K23 acetylation in HSCs and for expression of multipotency genes (Slamf1, Mecom, Hoxa9, Hlf, Gfi1, Egr, Gata3). Conditional Brpf1 knockout in hematopoietic cells, flow cytometry, H3K23ac immunoblotting, ROS and apoptosis assays, gene expression profiling The Journal of clinical investigation High 27500495
2016 De novo or inherited monoallelic BRPF1 mutations in humans impair H3K23 acetylation (measured in patient-derived cells and Brpf1-KO mouse lines), causing an intellectual disability syndrome. BRPF1 variants abolish or reduce acetyltransferase co-activation and some show aberrant subcellular localization. Patient variant functional assays, H3K23ac immunoblotting in patient fibroblasts and Brpf1-KO mice, localization studies American journal of human genetics High 27939639 27939640
2019 Crystal structure of the BRPF1 PZP domain bound to the H3 tail revealed that binding to extranucleosomal DNA dominates over H3-tail binding; both interactions are required for tight nucleosome core particle binding and for acetyltransferase function of the BRPF1-MORF-ING5-MEAF6 complex. X-ray crystallography of PZP–H3 complex, ITC binding assays, HAT activity assays Structure High 31711755
2020 BRPF1-KAT6A and BRPF1-KAT6B complexes catalyze H3K23 propionylation (in addition to acetylation) in vitro and in vivo; Brpf1 deletion obliterates both acylations in mouse embryos and fibroblasts. Pathogenic BRPF1 variants identified in 12 additional intellectual disability cases impair H3K23 propionylation. In vitro propionylation assays, mass spectrometry, immunofluorescence/ATAC-See in mouse embryos and fibroblasts, patient variant functional assays Science advances High 32010779
2020 The BRPF1 bromodomain acts as a selective reader of di-acetylated histone H4, preferentially binding H4K5acK8ac and H4K12acK8ac/K5ac; non-canonical regions of the bromodomain binding pocket (identified by NMR CSP and mutagenesis) mediate recognition of the second acetyl mark. ITC binding assays, NMR chemical shift perturbation, analytical ultracentrifugation, site-directed mutagenesis Current research in structural biology High 33554132
2009 In medaka fish, loss-of-function mutation in brpf1 (a MOZ HAT complex subunit) decreases Hox gene expression in pharyngeal arches and Zic gene expression posteriorly, causing craniofacial cartilage homeosis and caudal skeleton patterning defects; parallel MOZ-deficient mice display homologous craniofacial and cervical skeletal abnormalities with reduced Hox transcripts. Medaka forward genetics (biaxial symmetries mutant), in situ hybridization, mouse MOZ knockout Developmental biology High 19254709
1994 BR140 (BRPF1) was identified as a nuclear protein with zinc finger domains and homology to TAF250 (a TFIID subunit); it co-purified with an integrin and is broadly expressed, with highest abundance in testis and spermatogonia. cDNA cloning, sequence analysis, immunolocalization (subcellular fractionation/IHC), tissue Western blotting Biochemical and biophysical research communications Medium 7906940
2015 Structure-guided development of IACS-9571 yielded a dual TRIM24/BRPF1 bromodomain inhibitor (ITC Kd = 14 nM for BRPF1) whose binding mode was established by iterative X-ray co-crystal structures, enabling pharmacological interrogation of BRPF1 bromodomain function. X-ray co-crystallography (multiple structures), ITC, cellular target engagement assay Journal of medicinal chemistry High 26061247
2016 Twenty X-ray co-crystal structures of the BRPF1 bromodomain with diverse ligands revealed structural conservation of the acetyllysine-binding site, common binding motifs, and rare interactions including displacement of a conserved water molecule. High-throughput docking followed by X-ray crystallography of 20 BRPF1/ligand complexes Journal of medicinal chemistry High 27167503
2019 Brpf1 haploinsufficiency in mouse (Emx1-Cre heterozygotes) reduces dendritic complexity, spine density, and spine/synapse morphology in hippocampal granule cells and cortical pyramidal neurons, and decreases frequency and amplitude of miniature EPSCs, leading to impaired learning and memory. Conditional Brpf1 heterozygous mouse, morphological analysis, whole-cell patch clamp, behavioral assays Frontiers in cellular neuroscience High 31213987
2020 Isoform-specific functions of Brpf1 in hematopoietic stem and progenitor cells: Brpf1b promotes HSPC expansion while Brpf1a promotes quiescence; inhibition of Brpf1a by OF-1 increases histone acetylation and chromatin accessibility, upregulating self-renewal gene Mn1, and the expansion phenotype is rescued by Mn1 suppression. Bromodomain inhibitor chemical screen, isoform-specific overexpression/knockdown in HSPCs, chromatin accessibility (ATAC-seq), gene expression analysis, epistasis (Mn1 rescue) Journal of molecular cell biology Medium 31565729
2021 Brpf1 knockdown in hippocampal neurons reduces miniature EPSC frequency before changes in dendritic morphology appear; in vivo hippocampal Brpf1 knockdown impairs spatial learning; dysregulated genes include synaptic transmission regulators C1ql1, Grin2a, and others. shRNA knockdown in primary hippocampal neurons, whole-cell patch clamp (mEPSC recording), Morris water maze, RNA-seq Frontiers in cell and developmental biology Medium 34485298
2021 Brpf1 knockdown in MGE-derived GABAergic interneurons increases firing threshold, decreases evoked action potential number, and reduces miniature IPSC amplitude, demonstrating a key role of Brpf1 in inhibitory neurotransmission; differentiation into parvalbumin+ interneurons was not significantly changed. AAV-shBrpf1 knockdown, whole-cell patch clamp, immunofluorescence, MGE transplantation assay, RNA-seq G3 (Bethesda) Medium 33744924
2021 BRPF1 activates E2F2 and EZH2 expression by facilitating H3K14 acetylation at their promoters via the MOZ/MORF complex in hepatocellular carcinoma cells; BRPF1 ablation or pharmacological inhibition attenuates HCC cell growth in vitro and in vivo. BRPF1 gene ablation, pharmacological inhibition, ChIP-seq for H3K14ac, transcriptome sequencing, xenograft tumor models Communications biology Medium 34285329
2022 USP35 directly deubiquitinates and stabilizes BRPF1 protein; USP35-dependent BRPF1 accumulation enables BRPF1 to bind the SREBP2 promoter and activate SREBP2 transcription, thereby promoting mevalonate metabolism in prostate cancer cells. Co-IP/pulldown (USP35–BRPF1 interaction), ubiquitination assays, ChIP-qPCR (BRPF1 at SREBP2 promoter), rescue experiments Cell death discovery Medium 36357379
2023 BRPF1 associates with ERα on chromatin in breast cancer cells; BRPF1 blockade inhibits cell cycle progression, reduces chromatin accessibility, and silences ERα gene expression in antiestrogen-sensitive and -resistant cells, placing BRPF1 as an upstream regulator of estrogen signaling. ChIP-seq (BRPF1–ERα co-occupancy), ATAC-seq, transcriptome profiling, siRNA knockdown, pharmacological inhibition, patient-derived organoids Molecular cancer Medium 39113071
2023 Using site-specific photo-crosslinking with azide-acetyllysine in the BRPF1 bromodomain, the non-histone interactome of BRPF1 was mapped; interleukin enhancer-binding factor 3 (ILF3) was validated as a novel BRPF1 bromodomain interacting partner by ITC and co-IP. Unnatural amino acid photo-crosslinking, proteomics, ITC, co-immunoprecipitation The Journal of biological chemistry Medium 38072045
2023 BRPF1 bridges H3K4me3 and H3K23ac marks in human embryonic stem cells; BRPF1 deletion impairs H3K23ac and closes chromatin on stemness genes leading to hESC differentiation. Deletion of the N-terminal or PZP module abolishes BRPF1 function while PWWP deletion only partially impairs it. BRPF1 KO in hESCs, CUT&RUN/ChIP for H3K4me3 and H3K23ac, ATAC-seq, domain-deletion mutant functional rescue assays iScience Medium 36711238
2024 CaMKIIa-Cre-driven Brpf1 knockout in forebrain excitatory neurons reduces miniature EPSC frequency and downregulates genes related to synapse function (Pcdhgb1, Slc16a7, Robo3, Rho), impairing spatial and fear memory. Conditional Brpf1 KO (CaMKIIa-Cre), whole-cell patch clamp, RNA-seq, behavioral assays (fear conditioning, Morris water maze) Neural regeneration research Medium 37862219
2025 BRPF1 directly binds the ABCB1 promoter (CUT&RUN-qPCR) and enhances ABCB1 expression to confer multidrug resistance in Taxol-resistant TNBC; BRPF1 KO or inhibition reduces ABCB1 expression and suppresses ribosome biogenesis gene sets, sensitizing resistant cells to Taxol. CRISPR KO, pharmacological inhibition (PFI-4, OF-1), CUT&RUN-qPCR, RNA-seq, cell viability assays Experimental & molecular medicine Medium 40583060
2019 Truncated BRPF1, as found in human adult medulloblastoma patients with inactivating mutations, cooperates with SmoM2 activation to induce medulloblastoma in adult mice by promoting postmitotic neuron re-entry into the cell cycle via chromatin remodeling. In vivo mouse model (truncated BRPF1 + SmoM2 transgenic), cell cycle analysis, histology Cell reports Medium 31851932
2024 BRPF1 (as part of the MOZ/HBO1 complex) associates with NUP98 fusion oncoproteins on chromatin and within nuclear condensates; MYST HATs are molecular dependencies in NUP98-rearranged AML, and their inhibition decreases global H3K23ac, displaces NUP98::HOXA9 from chromatin at the Meis1 locus, and induces myeloid differentiation. Co-IP/proximity ligation assays (BRPF1–NUP98 FO association), ChIP-seq (H3K23ac, NUP98 occupancy), genetic inactivation, pharmacological inhibition, xenograft mouse models bioRxiv (preprint)preprint Medium bio_10.1101_2024.12.02.624182
2025 FBRSL1 binds upstream of the BRPF1 locus (via association with transcription factor YY1) and positively regulates BRPF1 expression; truncating FBRSL1 variants cause BRPF1 downregulation in patient blood and fibroblasts, and loss of Fbrsl1 in Xenopus disrupts brpf1 expression pattern. ChIP-seq (FBRSL1–YY1 at BRPF1 promoter), qRT-PCR in patient cells, Xenopus loss-of-function Human genetics Medium 40658195

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1. Nature structural & molecular biology 179 20400950
2015 Structure-Guided Design of IACS-9571, a Selective High-Affinity Dual TRIM24-BRPF1 Bromodomain Inhibitor. Journal of medicinal chemistry 127 26061247
2020 Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer. Science advances 89 32010779
2016 Mutations in the Chromatin Regulator Gene BRPF1 Cause Syndromic Intellectual Disability and Deficient Histone Acetylation. American journal of human genetics 85 27939640
2014 1,3-Dimethyl Benzimidazolones Are Potent, Selective Inhibitors of the BRPF1 Bromodomain. ACS medicinal chemistry letters 71 25408830
2013 Molecular insights into the recognition of N-terminal histone modifications by the BRPF1 bromodomain. Journal of molecular biology 67 24333487
2016 GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain. ACS medicinal chemistry letters 58 27326325
2016 Mutations in Histone Acetylase Modifier BRPF1 Cause an Autosomal-Dominant Form of Intellectual Disability with Associated Ptosis. American journal of human genetics 55 27939639
2015 Bivalent interaction of the PZP domain of BRPF1 with the nucleosome impacts chromatin dynamics and acetylation. Nucleic acids research 55 26626149
1994 BR140, a novel zinc-finger protein with homology to the TAF250 subunit of TFIID. Biochemical and biophysical research communications 55 7906940
2015 Deficiency of the chromatin regulator BRPF1 causes abnormal brain development. The Journal of biological chemistry 52 25568313
2009 Brpf1, a subunit of the MOZ histone acetyl transferase complex, maintains expression of anterior and posterior Hox genes for proper patterning of craniofacial and caudal skeletons. Developmental biology 48 19254709
2015 The lysine acetyltransferase activator Brpf1 governs dentate gyrus development through neural stem cells and progenitors. PLoS genetics 47 25757017
2015 The chromatin regulator Brpf1 regulates embryo development and cell proliferation. The Journal of biological chemistry 40 25773539
2021 Bromodomain-containing protein BRPF1 is a therapeutic target for liver cancer. Communications biology 38 34285329
2016 BRPF1 is essential for development of fetal hematopoietic stem cells. The Journal of clinical investigation 35 27500495
2014 Structural insights into recognition of acetylated histone ligands by the BRPF1 bromodomain. FEBS letters 32 25281266
2022 BRPF1-KAT6A/KAT6B Complex: Molecular Structure, Biological Function and Human Disease. Cancers 29 36077605
2020 Design, synthesis, and biological evaluation of dual targeting inhibitors of histone deacetylase 6/8 and bromodomain BRPF1. European journal of medicinal chemistry 28 32497960
2019 Molecular Basis for the PZP Domain of BRPF1 Association with Chromatin. Structure (London, England : 1993) 28 31711755
2016 Twenty Crystal Structures of Bromodomain and PHD Finger Containing Protein 1 (BRPF1)/Ligand Complexes Reveal Conserved Binding Motifs and Rare Interactions. Journal of medicinal chemistry 27 27167503
2019 BRPF1-associated intellectual disability, ptosis, and facial dysmorphism in a multiplex family. Molecular genetics & genomic medicine 26 31020800
2018 Structure-based discovery of selective BRPF1 bromodomain inhibitors. European journal of medicinal chemistry 24 29902720
2014 Expression atlas of the multivalent epigenetic regulator Brpf1 and its requirement for survival of mouse embryos. Epigenetics 24 24646517
2023 The MOZ-BRPF1 acetyltransferase complex in epigenetic crosstalk linked to gene regulation, development, and human diseases. Frontiers in cell and developmental biology 20 36712963
2020 The BRPF1 bromodomain is a molecular reader of di-acetyllysine. Current research in structural biology 19 33554132
2019 Brpf1 Haploinsufficiency Impairs Dendritic Arborization and Spine Formation, Leading to Cognitive Deficits. Frontiers in cellular neuroscience 19 31213987
2019 Novel BRPF1 mutation in a boy with intellectual disability, coloboma, facial nerve palsy and hypoplasia of the corpus callosum. European journal of medical genetics 18 31176769
2019 Truncated BRPF1 Cooperates with Smoothened to Promote Adult Shh Medulloblastoma. Cell reports 18 31851932
2020 Novel Missense Variant in Heterozygous State in the BRPF1 Gene Leading to Intellectual Developmental Disorder With Dysmorphic Facies and Ptosis. Frontiers in genetics 14 32457794
2020 A de novo BRPF1 variant in a case of Sudden Unexplained Death in Childhood. European journal of medical genetics 14 32652122
2022 Discovery, optimization and evaluation of 1-(indolin-1-yl)ethan-1-ones as novel selective TRIM24/BRPF1 bromodomain inhibitors. European journal of medicinal chemistry 13 35385803
2022 Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis. Cell death discovery 12 36357379
2021 Deficiency of Intellectual Disability-Related Gene Brpf1 Attenuated Hippocampal Excitatory Synaptic Transmission and Impaired Spatial Learning and Memory Ability. Frontiers in cell and developmental biology 11 34485298
2021 Transcriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade Gliomas. Frontiers in oncology 11 34926268
2024 Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory. Neural regeneration research 10 37862219
2024 Essential gene screening identifies the bromodomain-containing protein BRPF1 as a new actionable target for endocrine therapy-resistant breast cancers. Molecular cancer 10 39113071
2016 Development of small molecule inhibitors of BRPF1 and TRIM24 bromodomains. Drug discovery today. Technologies 10 27769360
2023 Pygo2 activates BRPF1 via Pygo2-H3K4me2/3 interaction to maintain malignant progression in colon cancer. Experimental cell research 9 37423512
2020 Isoform-specific involvement of Brpf1 in expansion of adult hematopoietic stem and progenitor cells. Journal of molecular cell biology 9 31565729
2022 BRPF1-associated syndrome: A patient with congenital ptosis, neurological findings, and normal intellectual development. American journal of medical genetics. Part A 8 35243762
2025 Epigenetic Regulation of Ferroptosis by the KDM3A/BRPF1 Transcriptional Axis Confers Neuroprotection in Postpartum Depression mouse model. Journal of affective disorders 6 40562111
2024 Enhanced cellular death in liver and breast cancer cells by dual BET/BRPF1 inhibitors. Protein science : a publication of the Protein Society 6 39473021
2023 BRPF1 bridges H3K4me3 and H3K23ac in human embryonic stem cells and is essential to pluripotency. iScience 6 36711238
2021 Deficiency of intellectual disability-related gene Brpf1 reduced inhibitory neurotransmission in MGE-derived GABAergic interneurons. G3 (Bethesda, Md.) 6 33744924
2023 Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Çanakkale with intellectual disability and dysmorphic facies: Case report and review of the literature. American journal of medical genetics. Part A 5 37190896
2014 Crystallization and preliminary X-ray diffraction analysis of the BRPF1 bromodomain in complex with its H2AK5ac and H4K12ac histone-peptide ligands. Acta crystallographica. Section F, Structural biology communications 5 25286946
1996 Gene BR140, which is related to AF10 and AF17, maps to chromosome band 3p25. Genes, chromosomes & cancer 5 8946209
2025 BRPF1 inhibition reduces migration and invasion of metastatic ovarian cancer cells, representing a potential therapeutic target. Scientific reports 4 40038391
2023 Integrated virtual screening and MD simulation approaches toward discovering potential inhibitors for targeting BRPF1 bromodomain in hepatocellular carcinoma. Journal of molecular graphics & modelling 4 37797430
2024 Broadening the ocular phenotypic spectrum of ultra-rare BRPF1 variants: report of two cases. Ophthalmic genetics 3 38590032
2024 The Phenotypic and Genotypic Spectrum of BRPF1-Related Disorder: 29 New Patients and Literature Review. Clinical genetics 3 39837771
2023 Development of 3-acetylindole derivatives that selectively target BRPF1 as new inhibitors of receptor activator of NF-κB ligand (RANKL)-Induced osteoclastogenesis. Bioorganic & medicinal chemistry 3 37951134
2025 Chromatin-focused genetic and chemical screens identify BRPF1 as a targetable vulnerability in Taxol-resistant triple-negative breast cancer. Experimental & molecular medicine 2 40583060
2025 FBRSL1 regulates the expression of chromatin regulators BRPF1 and KAT6A. Human genetics 2 40658195
2025 BRPF1 in cancer epigenetics: a key regulator of histone acetylation and a promising therapeutic target. Cell death discovery 2 41053095
2023 Uncovering the non-histone interactome of the BRPF1 bromodomain using site-specific azide-acetyllysine photochemistry. The Journal of biological chemistry 2 38072045
2022 Computational studies with flavonoids and terpenoids as BRPF1 inhibitors: in silico biological activity prediction, molecular docking, molecular dynamics simulations, MM/PBSA calculations. SAR and QSAR in environmental research 2 35822928
2013 [BRPF2, a novel transcript of BRPF1 and their expression in mice tissues]. Yi chuan = Hereditas 1 23357268
2026 GPX8+ cancer-associated fibroblast-derived lactate contributes to lenvatinib resistance by facilitating BRPF1 expression through histone H3 lysine 18 lactylation in hepatocellular carcinoma. Oncogene 0 42174112
2025 Ocular findings of BRPF1 variants: a case report and literature review. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus 0 40752867
2025 BRPF1 inhibitor GSK6853 inhibits NSCLC cell proliferation via the JAK2/STAT3/CCNA2 axis to induce cell cycle arrest. Investigational new drugs 0 41160097

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