Affinage

BPTF

Nucleosome-remodeling factor subunit BPTF · UniProt Q12830

Length
3046 aa
Mass
338.3 kDa
Annotated
2026-04-28
94 papers in source corpus 38 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BPTF is the scaffolding subunit of the NURF ATP-dependent chromatin remodeling complex, where it couples histone modification readout to nucleosome sliding and transcriptional activation at promoters and enhancers. Its C-terminal PHD finger recognizes H3K4me3 — with binding modulated by H3 tail–DNA contacts on nucleosomes — while its bromodomain engages acetylated histones including H4K16ac and diacetylated H2A.Z, enabling multivalent recruitment of the ISWI/SMARCA1 ATPase to appropriately marked chromatin (PMID:16728978, PMID:29648537, PMID:28771339, PMID:11583616). BPTF physically interacts with and facilitates chromatin occupancy of sequence-specific transcription factors including c-MYC, MYCN, Smad2, AR/FOXA1, and NF-κB p50, thereby integrating signal-dependent transcription factor activity with chromatin remodeling at target loci (PMID:26729287, PMID:26041917, PMID:41381516, PMID:31934287). Through maintenance of chromatin accessibility, BPTF is essential for hematopoietic stem cell self-renewal, mammary stem cell differentiation, T cell homeostasis, and proper mammalian embryogenesis — including trophoblast and visceral endoderm specification — and its loss suppresses MYC-driven tumorigenesis and enhances tumor immunogenicity by upregulating antigen processing and natural cytotoxicity receptor ligands (PMID:29456179, PMID:28579392, PMID:27799308, PMID:18974875, PMID:26729287, PMID:27651309, PMID:39935175).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1999 Medium

    Establishing that BPTF (FAC1) DNA-binding activity is post-translationally regulated answered whether BPTF function is constitutive or dynamically controlled, revealing phosphorylation as a regulatory input.

    Evidence EMSA with phosphatase treatment and pharmacological phosphatase inhibition in nuclear extracts

    PMID:10403843

    Open questions at the time
    • kinase(s) responsible not identified
    • in vivo relevance of phosphorylation-dependent binding not tested
    • phosphorylation sites on BPTF not mapped
  2. 2000 Medium

    Identification of BPTF interaction with the zinc-finger protein ZF87/MAZ and demonstration that BPTF represses MAZ-driven transcription established that BPTF can modulate transcription factor activity through direct protein-protein contact.

    Evidence Yeast two-hybrid, recombinant protein interaction, deletion mapping, and co-transfection reporter assay

    PMID:10727212

    Open questions at the time
    • no in vivo confirmation of BPTF-MAZ functional interaction
    • relevance to endogenous gene targets not shown
  3. 2001 High

    Reconstitution of the NURF complex showed that BPTF together with ISWI is necessary and sufficient for nucleosome sliding, defining BPTF as the essential scaffolding subunit that also mediates transcription factor recruitment.

    Evidence Reconstitution from recombinant Drosophila proteins with in vitro nucleosome sliding and transcription factor interaction assays

    PMID:11583616

    Open questions at the time
    • mammalian BPTF-ISWI sufficiency for sliding not directly reconstituted at this point
    • mechanism by which the HMGA-like domain facilitates sliding not structurally resolved
  4. 2006 High

    Structural determination of the BPTF PHD finger bound to H3K4me3 established the molecular basis for how NURF reads this activating histone mark, revealing the specificity pocket architecture and key residues.

    Evidence X-ray crystallography and NMR of the PHD finger free and H3K4me3-bound, with mutagenesis validation

    PMID:16728978

    Open questions at the time
    • how PHD finger engagement translates to remodeling activity not addressed
    • contribution of bromodomain in multivalent binding not yet characterized
  5. 2006 Medium

    Genetic studies in C. elegans showed that a BPTF ortholog (NURF-1) functions in a NURF-like complex to antagonize repressive chromatin complexes during cell-fate specification, establishing an evolutionarily conserved role in developmental gene regulation.

    Evidence Genetic suppressor screen and epistasis analysis in C. elegans vulval development

    PMID:16774993

    Open questions at the time
    • biochemical confirmation of a C. elegans NURF complex not provided
    • direct chromatin targets not identified
  6. 2008 High

    Knockout studies in mouse established that BPTF is essential for mammalian embryogenesis, specifically for trophoblast differentiation, visceral endoderm specification, and gastrulation, and that it physically interacts with Smad2/3 to co-regulate TGF-β target genes.

    Evidence Bptf-null mouse embryos with histological and molecular characterization; co-immunoprecipitation with Smad factors

    PMID:18794365 PMID:18974875

    Open questions at the time
    • direct genomic targets of BPTF-Smad co-regulation in embryo not mapped
    • whether NURF remodeling activity per se is required for these phenotypes not tested
  7. 2009 High

    Characterization of alternatively spliced Drosophila NURF301 isoforms showed that the PHD finger and bromodomain are dispensable for some NURF functions but required for spermatogenesis, demonstrating that distinct BPTF isoforms confer different chromatin-reading capabilities.

    Evidence Isoform analysis, histone mark binding assays, and genetic mutant phenotyping in Drosophila

    PMID:19629165

    Open questions at the time
    • mammalian BPTF isoform-specific functions not yet delineated
    • whether truncated isoforms have distinct genomic targets not determined
  8. 2015 High

    Discovery that BPTF physically interacts with c-MYC and is required for MYC-driven transcription, proliferation, and in vivo tumorigenesis established BPTF as a critical MYC cofactor linking chromatin remodeling to oncogenic programs.

    Evidence Co-IP, ChIP-seq, Bptf-null MEFs, and Bptf-deleted pancreatic tumor mouse model

    PMID:26729287

    Open questions at the time
    • structural basis of the BPTF-MYC interaction unknown
    • whether BPTF is required for all MYC target genes or a specific subset not fully resolved
  9. 2015 High

    Demonstration that BPTF cooperates with phospho-Smad2 to open chromatin and activate wnt8a in zebrafish neural posteriorization provided in vivo evidence for BPTF as a signal-responsive chromatin remodeling effector.

    Evidence Morpholino knockdown, Co-IP, ChIP showing nucleosome density changes at wnt8a promoter in zebrafish

    PMID:26041917

    Open questions at the time
    • genome-wide targets of BPTF-Smad2 in neural development not mapped
  10. 2016 Medium

    Conditional knockout studies revealed cell-intrinsic roles of BPTF in T cell homeostasis and Treg function, and showed that BPTF suppresses tumor immunogenicity by repressing immunoproteasome and antigen transporter genes, linking chromatin remodeling to immune evasion.

    Evidence T cell- and Treg-specific Bptf conditional KO mice; shRNA KD with gene expression analysis and PSMB8 inhibitor rescue

    PMID:27651309 PMID:27799308

    Open questions at the time
    • whether BPTF directly binds immunoproteasome gene promoters or acts indirectly not fully resolved
    • mechanism connecting NURF remodeling to Foxp3 regulation unknown
  11. 2017 High

    ATAC-seq studies demonstrated that BPTF maintains open chromatin specifically at enhancer regions in mammary epithelial cells and is required for mammary stem cell self-renewal, providing genome-wide evidence for its role in stem cell chromatin accessibility.

    Evidence shRNA KD and chemical inhibition with ATAC-seq and mammary repopulation assays

    PMID:28579392

    Open questions at the time
    • whether BPTF acts at enhancers via NURF-dependent sliding or additional mechanisms not distinguished
  12. 2018 High

    NMR and MD studies revealed that H3 tail–DNA contacts within nucleosomes inhibit BPTF PHD finger binding, and that post-translational modifications relieve this autoinhibition, resolving why histone peptide binding affinities overestimate nucleosomal recognition.

    Evidence NMR spectroscopy and MD simulations comparing BPTF PHD binding to free peptides versus reconstituted nucleosomes

    PMID:29648537

    Open questions at the time
    • which specific modifications most effectively relieve autoinhibition on native chromatin not systematically tested
    • in vivo validation of this regulatory mechanism lacking
  13. 2018 High

    Hematopoietic-specific BPTF deletion showed it is essential for HSC maintenance and long-term reconstitution, with loss of chromatin accessibility at stemness genes, establishing BPTF as a master regulator of adult stem cell identity.

    Evidence Conditional KO mice with bone marrow reconstitution, RNA-seq, and ATAC-seq

    PMID:29456179

    Open questions at the time
    • whether BPTF maintains HSC identity through NURF-dependent remodeling or additional transcription factor interactions not dissected
  14. 2018 Medium

    Biophysical characterization showed the BPTF bromodomain recognizes diacetylated H2A.Z, expanding the reader repertoire beyond canonical H3/H4 marks to histone variants.

    Evidence PrOF NMR, CPMG NMR, photo-crosslinking, and fluorescence anisotropy with acetylated H2A.Z peptides

    PMID:28771339

    Open questions at the time
    • weak affinity (Kd ~780 µM) raises question of physiological relevance
    • nucleosome-context validation of H2A.Z recognition not performed in this study
  15. 2020 Medium

    Genetic epistasis in the Eµ-Myc lymphoma model confirmed BPTF haploinsufficiency delays MYC-driven lymphomagenesis and showed compensatory NF-κB pathway activation, establishing BPTF as a dose-dependent MYC effector in vivo.

    Evidence Eµ-Myc transgenic mice with conditional Bptf deletion, gene expression profiling

    PMID:32451433

    Open questions at the time
    • whether NF-κB activation is a direct consequence of BPTF loss or secondary not resolved
  16. 2020 Medium

    hnRNPLL was found to control alternative splicing of Bptf during ES cell differentiation, showing that BPTF isoform switching is a regulated event important for pluripotency exit.

    Evidence Functional RBP screen, hnRNPLL KO mice, RNA-seq and splicing analysis

    PMID:33349972

    Open questions at the time
    • functional differences between ES cell-preferred and differentiation-preferred BPTF isoforms not biochemically characterized
  17. 2024 High

    Integrated genomic and biochemical analysis in prostate cancer demonstrated that BPTF interacts with AR through its bromodomain and forms a ternary complex with FOXA1, using NURF remodeling to increase chromatin accessibility at AR binding sites — resolving how BPTF couples to hormone-dependent transcription.

    Evidence Co-IP, ChIP-seq, ATAC-seq, RNA-seq, and bromodomain inhibitor treatment in prostate cancer cells

    PMID:41381516

    Open questions at the time
    • whether the BPTF-AR interaction is acetylation-dependent on AR itself not determined
    • structural basis of the ternary BPTF-AR-FOXA1 complex unknown
  18. 2025 Medium

    Identification that BPTF PHD-finger reading of H3K4me3 on tumor cells suppresses NK cell recognition, and that PROTAC-mediated BPTF degradation restores NCR ligand surface expression to enhance anti-tumor immunity, validated BPTF as a druggable immune-evasion target.

    Evidence PROTAC degrader, NK cytotoxicity assays, flow cytometry, and in vivo xenograft models

    PMID:39935175

    Open questions at the time
    • mechanism linking BPTF-H3K4me3 reading to NCR ligand gene repression not fully elucidated
    • PROTAC selectivity and off-target effects not comprehensively assessed
  19. 2025 Medium

    Planarian stem cell studies and nucleosome mass spectrometry established that BPTF preferentially maintains accessibility at Set1-dependent (broad H3K4me3) promoters and requires coincident H3K4me3 with K9ac, K14ac, and K18ac for effective nucleosome engagement, defining the combinatorial histone code read by the tandem PHD-bromodomain cassette.

    Evidence RNAi + ATAC-seq in planarians; nucleosome mass spectrometry with defined modification states (preprint for Nuc-MS)

    PMID:40069606 PMID:bio_10.1101_2025.05.01.651740

    Open questions at the time
    • Nuc-MS data is preprint and awaits peer review
    • whether broad versus narrow H3K4me3 distinction applies in mammalian BPTF function not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for how BPTF scaffolds the NURF complex and how its multivalent histone reading is allosterically coupled to ISWI ATPase activation remains unresolved at atomic resolution.
  • no cryo-EM or crystal structure of mammalian NURF holo-complex
  • mechanism coupling histone modification readout to ATPase stimulation unknown
  • systematic identification of BPTF isoform-specific interactomes and genomic targets in mammalian tissues not performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0042393 histone binding 7 GO:0098772 molecular function regulator activity 3 GO:0003677 DNA binding 2
Localization
GO:0005694 chromosome 8 GO:0005634 nucleus 3
Pathway
R-HSA-4839726 Chromatin organization 9 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4
Partners
ARFOXA1MYCMYCNNFKB1PHF6SMAD2SMARCA1
Complex memberships
NURF

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 The PHD finger of BPTF specifically recognizes histone H3 trimethylated at K4 (H3K4me3) through anti-parallel beta-sheet formation on the PHD finger surface, with the long side chains of R2 and K4me3 fitting into adjacent pre-formed surface pockets bracketing an invariant tryptophan. Crystal and NMR structures of the bromodomain-proximal PHD finger in free and H3K4me3-bound states were determined, and key specificity-determining residues were identified by point mutagenesis. X-ray crystallography, NMR spectroscopy, peptide binding assays, PHD finger point mutagenesis Nature High 16728978
2001 BPTF (NURF301), the largest subunit of the NURF complex, together with the ISWI ATPase is necessary and sufficient for accurate and efficient nucleosome sliding in vitro. An HMGA/HMGI(Y)-like domain of NURF301 facilitates nucleosome sliding, implicating DNA conformational changes in the sliding mechanism. NURF301 also directly interacts with sequence-specific transcription factors, providing a basis for targeted recruitment of the NURF complex to specific genes. Reconstitution of full and partial NURF complexes from recombinant proteins, in vitro nucleosome sliding assay, interaction studies with transcription factors Molecular cell High 11583616
2009 In Drosophila, alternative splicing of NURF301/BPTF generates distinct NURF complexes with differing histone modification binding specificities. Full-length NURF301 contains a C-terminal bromodomain and PHD finger that bind H3K4me3 and H4K16Ac respectively; a truncated isoform lacking these domains assembles a complex deficient in these marks. Full-length NURF301 (but not the truncated isoform) is required for spermatogenesis and expression of spermatid differentiation genes. Isoform characterization, microarray expression profiling, genetic mutant analysis, chromatin reader binding assays PLoS genetics High 19629165
2018 The conformation of histone H3 tails within nucleosomes is inhibitory to BPTF PHD finger binding. The H3 tails interact robustly but dynamically with nucleosomal DNA, substantially reducing PHD finger association compared to free peptide. Altering the electrostatics of the H3 tail via post-translational modification or mutation increases accessibility to the PHD finger, indicating that PTM crosstalk regulates effector domain binding by altering nucleosome conformation. NMR spectroscopy, molecular dynamics (MD) simulations, binding assays with nucleosomes vs. peptides eLife High 29648537
2008 Bptf is required in mouse embryos for establishment of a functional distal visceral endoderm and proper gastrulation. Bptf-null embryos implant but fail to establish anterior visceral endoderm and primitive streak. Bptf physically and functionally interacts with Smad transcription factors (Smad2/3) and may co-regulate gene targets of the TGF-β/Smad pathway essential for early mouse development. Knockout mouse analysis, lineage marker histology, microarray, embryoid body differentiation assays, co-immunoprecipitation (physical link to Smad factors) PLoS genetics High 18974875
2008 BPTF/FAC1 is essential for trophoblast differentiation during early mouse development; its loss causes failure of ectoplacental cone development and embryonic lethality by E6.5. Development of the anterior visceral endoderm and primitive streak is also impaired in BPTF-null embryos. Loss-of-function mouse allele, histological analysis with lineage markers Molecular and cellular biology High 18794365
2015 BPTF physically interacts with c-MYC and is required for the full c-MYC transcriptional program in fibroblasts. BPTF knockdown leads to decreased c-MYC recruitment to DNA and changes in chromatin accessibility. In Bptf-null MEFs, BPTF is necessary for c-MYC-driven proliferation, G1-S progression, and replication stress but not c-MYC-driven apoptosis. In vivo, Bptf inactivation in pre-neoplastic pancreatic acinar cells significantly delays tumor development. Co-immunoprecipitation, ChIP-seq (chromatin accessibility), genetic KO MEFs, in vivo mouse tumor model Nature communications High 26729287
2015 In zebrafish, Bptf physically and functionally interacts with phospho-Smad2 (activated by non-Nodal TGF-β signaling) to promote expression of wnt8a, a critical gene for neural posteriorization. Bptf and Smad2 directly bind to and activate the wnt8a promoter by recruiting the NURF remodeling complex, and loss of Bptf increases nucleosome density on the wnt8a promoter. Morpholino knockdown in zebrafish, co-immunoprecipitation, ChIP (nucleosome density and factor binding at wnt8a promoter), reporter assays The Journal of neuroscience High 26041917
2017 BPTF maintains chromatin accessibility at enhancer regions in mammary epithelial cells (MECs) and is essential for mammary gland stem cell (MaSC) self-renewal and differentiation. BPTF depletion arrests cells at an undefined stage of epithelial differentiation with incapacity to achieve luminal cell fate, associated with loss of open chromatin at enhancers. shRNA-mediated KD, ATAC-seq (genome-wide DNA accessibility), BPTF chemical inhibition, mammary repopulation assays Stem cell reports High 28579392
2018 The BPTF bromodomain directly interacts with histone variant H2A.Z in a diacetylation-dependent manner (highest affinity for K4ac/K11ac diacetylation, Kd ~780 µM). This interaction was confirmed by protein-observed 19F NMR (PrOF NMR), 1H NMR CPMG experiments, and photo-cross-linking, and shows specificity over a panel of other bromodomains. PrOF NMR, CPMG NMR relaxation, photo-cross-linking, fluorescence anisotropy, peptide binding assays Biochemistry Medium 28771339
2016 MITF directly transcriptionally activates BPTF expression by binding to the BPTF promoter in melanoma cells, as shown by ChIP and luciferase reporter assays. BPTF transduces MITF-driven pro-survival signals including activation of BCL2, and BPTF overexpression rescues growth suppression caused by MITF silencing. ChIP, luciferase reporter assay, shRNA knockdown, cDNA rescue experiments Proceedings of the National Academy of Sciences of the United States of America Medium 27185926
2016 BPTF is required for T cell homeostasis via a cell-intrinsic mechanism, and Treg cell-specific BPTF deletion leads to reduced Foxp3 expression, increased lymphocyte infiltration in non-lymphoid organs, and systemic autoimmune syndrome in mice. Conditional T cell-specific and Treg-specific Bptf knockout mice, flow cytometry, histology Journal of immunology Medium 27799308
2016 NURF (via BPTF) directly regulates expression of immunoproteasome subunit genes Psmb8 and Psmb9 and antigen transporter genes Tap1 and Tap2. BPTF silencing enhances tumor antigenicity through improved antigen processing, and PSMB8 inhibitor ONX-0914 reverses the effects of BPTF ablation. shRNA knockdown, gene expression analysis, PSMB8 inhibitor rescue experiments, co-culture cytotoxicity assays Cancer research Medium 27651309
2017 BPTF occupies heparanase (Hpse) regulatory elements and activates its expression, leading to increased heparanase activity, reduced cell surface abundance of heparan sulfate proteoglycans (HSPGs) and natural cytotoxicity receptor (NCR) co-ligands, thereby suppressing NK cell cytolytic activity against tumor cells. ChIP (BPTF at heparanase promoter), gain/loss-of-function experiments, in vivo NCR1 blocking, NK cell cytotoxicity assays Oncotarget Medium 28969075
2018 BPTF is required for maintaining the population of hematopoietic stem/progenitor cells (HSPCs) and long-term HSCs. Bptf-deficient HSCs are defective in reconstituted hematopoiesis. BPTF loss downregulates HSC-specific gene programs including master transcription factors Meis1, Pbx1, Mn1, and Lmo2, and reduces chromatin accessibility at key HSC 'stemness' genes. Conditional knockout mice (hematopoietic-specific), bone marrow reconstitution assays, RNA-seq, ATAC-seq Stem cell reports High 29456179
2018 The lncRNA NMR directly binds to BPTF and recruits BPTF to chromatin to potentially promote expression of MMP3 and MMP10 via the ERK1/2 pathway in esophageal squamous cell carcinoma cells. RNA pulldown, Co-IP, ChIP Cancer letters Medium 29763634
2019 BPTF cooperates with the p50 subunit of NF-κB to regulate COX-2 promoter activity and expression in lung cancer cells. BPTF is identified as a COX-2 promoter-binding protein by biotin-streptavidin-agarose pulldown and ChIP; BPTF knockdown abrogates p50 binding to the COX-2 promoter, and p50 inhibition reverses the effect of BPTF silencing on COX-2 expression. Biotin-streptavidin-agarose pulldown, mass spectrometry, ChIP, co-immunoprecipitation, luciferase reporter assay American journal of translational research Medium 31934287
2000 FAC1 (BPTF) interacts with the Myc-associated zinc finger protein ZF87/MAZ, as demonstrated by yeast two-hybrid and confirmed with recombinant protein in vitro. The ZF87/MAZ interaction domain was mapped to the region containing a putative NLS/NES of FAC1. FAC1 represses ZF87/MAZ-induced transcriptional activation of the SV40 promoter in a dose-dependent manner, and a FAC1 deletion mutant lacking the ZF87/MAZ interaction domain does not suppress ZF87/MAZ activation. Yeast two-hybrid, in vitro recombinant protein interaction, deletion mutant mapping, co-transfection luciferase reporter assay Biochemistry Medium 10727212
1999 FAC1 (BPTF) DNA binding activity is dramatically enhanced by phosphorylation; phosphatase treatment of nuclear extracts reduces FAC1 DNA binding affinity, and inhibition of serine/threonine phosphatases increases FAC1 DNA binding activity, indicating that FAC1 DNA binding is regulated by phosphorylation. DNA binding assays (EMSA), phosphatase treatment of nuclear extracts, pharmacological phosphatase inhibition Biochemical and biophysical research communications Medium 10403843
2022 BPTF directly binds to the Cdc25A promoter (-178/+107 region) and transcriptionally activates Cdc25A expression, accelerating the cell cycle in colorectal cancer cells. BPTF itself is transcriptionally regulated by c-Myc, forming a c-Myc/BPTF/Cdc25A signaling axis. RNA-seq, DNA-pulldown, ChIP, luciferase reporter assay, siRNA/shRNA knockdown Redox biology Medium 35932692
2021 METTL14-mediated m6A modification negatively regulates the mRNA stability of BPTF. METTL14 deficiency leads to accumulation of BPTF, which remodels the enhancer landscape and constitutes super-enhancers activating downstream oncogenic targets such as ENO2 and SRC, leading to glycolytic reprogramming in renal cell carcinoma. MeRIP-seq, RNA-seq, ChIP-seq, ATAC-seq, cell line and organoid models, xenograft models Theranostics Medium 33664855
2020 hnRNPLL controls alternative splicing of Bptf during embryonic stem cell differentiation, promoting ES cell-preferred exon skipping events. hnRNPLL-mediated alternative splicing of Bptf (and Tbx3) is important for pluripotency exit; depletion of hnRNPLL leads to sustained expression of ES cell-preferred Bptf isoforms and differentiation deficiency. Functional RBP screen, hnRNPLL knockout mice, RNA-seq, splicing analysis The EMBO journal Medium 33349972
2019 BPTF's impact on high-grade glioma growth is mediated through positive effects on expression of MYC and MYC pathway targets, as shown by shRNA screens in vitro/in vivo. BPTF depletion reduces tumor self-renewal capacity and leads to more neuronal characteristics. In vitro/in vivo epigenomic shRNA inhibition screen, gene expression analysis, neurosphere self-renewal assays Oncogene Medium 31844250
2024 BPTF interacts with MYCN and core regulatory circuitry (CRC) transcription factors in neuroblastoma, as shown by immunoprecipitation/mass spectrometry. Genome-wide BPTF distribution shows dual roles: co-localization with MYCN/MYC at cell cycle gene promoters, and co-localization with CRC transcription factors at super-enhancers to regulate cell identity. Immunoprecipitation/mass spectrometry, bulk RNA-seq, single-cell sequencing, ChIP-seq, tissue microarrays bioRxivpreprint Medium 38405949
2024 BPTF regulates androgen receptor (AR) activity in prostate cancer by increasing chromatin accessibility at AR binding sites (through SMARCA1, the catalytic NURF subunit) and by forming a protein complex with AR and FOXA1 in which FOXA1 recruits the BPTF-AR complex to chromatin while BPTF stabilizes the AR-FOXA1 interaction. BPTF interacts with AR through its bromodomain, and bromodomain inhibition disrupts this interaction and impairs AR signaling. RNA-seq, ChIP-seq, ATAC-seq, Co-IP, bromodomain inhibitor treatment, BPTF knockdown Nature communications High 41381516
2025 BPTF's PHD finger interprets H3K4me3 on HCC cells to hinder their recognition by NK cells. PROTAC-mediated degradation of BPTF directly enhances the abundance of natural cytotoxicity receptor ligands on HCC cells, facilitating recognition and cytotoxicity by NK cells both in vitro and in vivo. PROTAC degrader, NK cell cytotoxicity assays, flow cytometry for NCR ligand expression, in vivo xenograft models Molecular therapy Medium 39935175
2020 BPTF is required for normal B-cell differentiation and c-MYC-driven B-cell lymphomagenesis. Haploinsufficiency of Bptf delays lymphomagenesis in Eμ-Myc mice. Tumors arising in a Bptf heterozygous background display decreased c-MYC levels and pathway activity, and increased NF-κB pathway activation. Eμ-Myc transgenic mouse model with conditional Bptf deletion, gene expression analysis Oncogene Medium 32451433
2023 PHF6 physically interacts with BPTF and recruits it to mediate epigenetic remodeling to augment HIF transcriptional activity in breast cancer cells. PHF6 also physically interacts with HIF-1α and HIF-2α to potentiate HIF-driven transcriptional events. Co-immunoprecipitation, ChIP-qPCR, CRISPR HIF double knockout Journal of translational medicine Medium 36967443
2022 BPTF promotes COX-2 expression by facilitating VEGF promoter occupancy; lumbrokinase downregulates BPTF expression, decreases its anchoring at the VEGF promoter region, and thereby suppresses VEGF expression in NSCLC cells. ChIP (BPTF at VEGF promoter), Western blot, siRNA knockdown Biomolecules Low 39062456
2024 NUP98-BPTF fusion protein promotes transformation of NIH3T3 fibroblasts by transcriptionally upregulating Pim1 through binding to its promoter, and activates MYC and mTORC1 signaling. PIM1 knockdown or pharmacological mTORC1 inhibition suppresses NUP98-BPTF-induced transformation. NUP98-BPTF also enhances survival of Jurkat T-ALL cells by inactivating the pro-apoptotic protein BAD. Lentiviral inducible expression in NIH3T3 and Jurkat cells, ChIP (binding to Pim1 promoter), shRNA/inhibitor rescue experiments Cancer medicine Medium 38940430
2025 Molecular dynamics simulations reveal that BPTF PHD finger and bromodomain adopt distinct conformational states depending on binding context; nucleosome engagement induces compaction of the multidomain structure. PHD finger binding displaces the H3 tail from nucleosomal DNA, increasing H3 tail flexibility and promoting compensatory binding of the H4 tail to DNA, weakening overall hydrogen bonding with DNA and suggesting localized nucleosome destabilization. Molecular dynamics (MD) simulations Biophysical journal Low 40616262
2025 Using nucleosome mass spectrometry, the BPTF PHD-bromodomain native tandem reader was shown to require coincident H3K4me3 together with K9ac, K14ac, and K18ac for effective nucleosome engagement, demonstrating multivalent combinatorial histone modification readout. Nucleosome mass spectrometry (Nuc-MS), native top-down MS bioRxiv (preprint)preprint Medium bio_10.1101_2025.05.01.651740
2024 BPTF activates hTERT expression transcriptionally in hepatocellular carcinoma cells, as shown by knockdown experiments demonstrating that BPTF loss reduces hTERT expression and inhibits stem cell traits and tumor growth. shRNA knockdown, Western blot, xenograft mouse model Redox biology Low 30419422
2024 BPTF regulates FOXC1 protein stability in glioma via USP34-mediated de-ubiquitination; BPTF knockdown reduces FOXC1 protein levels and inhibits glioma cell proliferation, apoptosis, and migration. The interaction between BPTF and USP34, and the effect on FOXC1 ubiquitination, was demonstrated by immunoprecipitation assays. Co-immunoprecipitation, ubiquitination assay, Western blot, shRNA knockdown, functional cell assays Histology and histopathology Low 38686761
2025 BPTF primarily affects chromatin accessibility at gene promoters near transcription start sites in planarian stem cells; BPTF-dependent loss of accessibility and gene expression is greatest at genes marked by Set1-dependent H3K4me3 (with broader peaks) but not MLL1/2-dependent H3K4me3. Loss of bptf phenocopies Set1 knockdown. RNAi knockdown in planarians, ATAC-seq, RNA-seq, genetic epistasis with Set1 BMC genomics Medium 40069606
2025 BPTF bromodomain directly interacts with acetylated H2A.Z isoforms in an affinity-dependent and acetyl-lysine binding pocket-specific manner, as validated by photoaffinity probes with diazirine photo-crosslinking in both recombinant BPTF and in nuclear lysates from A549 lung cancer cells. Endogenous BPTF was enriched by acetylated H2A.Z probes, though to a lesser extent than the canonical H4K16ac partner. Photoaffinity crosslinking probes, SDS-PAGE, pulldown from nuclear lysates, bottom-up proteomics for histone acetylation quantification Biochemistry Medium 40864556
2024 BPTF binds directly to the promoter region of the Slug gene and activates Slug transcription, thereby promoting trophoblast epithelial-to-mesenchymal transition (EMT). BPTF knockdown prevents EMT and attenuates trophoblast invasion in vitro. shRNA knockdown, ChIP (BPTF at Slug promoter), invasion assays Gene Low 38521110
2006 In C. elegans, ISW-1 (ISWI ortholog) acts as part of a NURF-like complex with NURF-1 (NURF301/BPTF ortholog) to promote vulval cell-fate specification by antagonizing the transcriptional activities of Myb-MuvB/dREAM, NuRD, and Tip60/NuA4 complexes. Mutations in isw-1 and nurf-1 suppress both the synMuv phenotype and the multivulva phenotype caused by Ras pathway overactivation. Genetic suppressor screen, double-mutant epistasis analysis in C. elegans Development Medium 16774993

Source papers

Stage 0 corpus · 94 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Molecular basis for site-specific read-out of histone H3K4me3 by the BPTF PHD finger of NURF. Nature 642 16728978
2001 Dual functions of largest NURF subunit NURF301 in nucleosome sliding and transcription factor interactions. Molecular cell 207 11583616
2022 Hypoxia-induced exosomal circPDK1 promotes pancreatic cancer glycolysis via c-myc activation by modulating miR-628-3p/BPTF axis and degrading BIN1. Journal of hematology & oncology 136 36068586
2008 Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells. PLoS genetics 126 18974875
2018 The conformation of the histone H3 tail inhibits association of the BPTF PHD finger with the nucleosome. eLife 123 29648537
2018 Novel long noncoding RNA NMR promotes tumor progression via NSUN2 and BPTF in esophageal squamous cell carcinoma. Cancer letters 118 29763634
2018 Circ-BPTF promotes bladder cancer progression and recurrence through the miR-31-5p/RAB27A axis. Aging 106 30103209
2016 BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis. Nature communications 103 26729287
2021 Downregulated METTL14 accumulates BPTF that reinforces super-enhancers and distal lung metastasis via glycolytic reprogramming in renal cell carcinoma. Theranostics 102 33664855
2015 The role of BPTF in melanoma progression and in response to BRAF-targeted therapy. Journal of the National Cancer Institute 84 25713167
2017 Haploinsufficiency of the Chromatin Remodeler BPTF Causes Syndromic Developmental and Speech Delay, Postnatal Microcephaly, and Dysmorphic Features. American journal of human genetics 74 28942966
2015 Dual Screening of BPTF and Brd4 Using Protein-Observed Fluorine NMR Uncovers New Bromodomain Probe Molecules. ACS chemical biology 67 26158404
2006 C. elegans ISWI and NURF301 antagonize an Rb-like pathway in the determination of multiple cell fates. Development (Cambridge, England) 59 16774993
2000 Identification and characterization of BPTF, a novel bromodomain transcription factor. Genomics 59 10662542
1995 FAC1, a novel gene identified with the monoclonal antibody Alz50, is developmentally regulated in human brain. Developmental neuroscience 55 7621746
2010 A novel translocation breakpoint within the BPTF gene is associated with a pre-malignant phenotype. PloS one 51 20300178
2018 BPTF promotes hepatocellular carcinoma growth by modulating hTERT signaling and cancer stem cell traits. Redox biology 50 30419422
2017 BPTF Maintains Chromatin Accessibility and the Self-Renewal Capacity of Mammary Gland Stem Cells. Stem cell reports 49 28579392
2009 Alternative splicing of NURF301 generates distinct NURF chromatin remodeling complexes with altered modified histone binding specificities. PLoS genetics 44 19629165
2008 Transcriptional regulator BPTF/FAC1 is essential for trophoblast differentiation during early mouse development. Molecular and cellular biology 38 18794365
2018 The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program Essential for the Maintenance of Adult Hematopoietic Stem Cells. Stem cell reports 36 29456179
2016 BPTF transduces MITF-driven prosurvival signals in melanoma cells. Proceedings of the National Academy of Sciences of the United States of America 34 27185926
2019 circCTIC1 promotes the self-renewal of colon TICs through BPTF-dependent c-Myc expression. Carcinogenesis 33 30403769
2000 Fetal Alz-50 clone 1 (FAC1) protein interacts with the Myc-associated zinc finger protein (ZF87/MAZ) and alters its transcriptional activity. Biochemistry 32 10727212
2019 BPTF regulates growth of adult and pediatric high-grade glioma through the MYC pathway. Oncogene 31 31844250
2017 BPTF inhibits NK cell activity and the abundance of natural cytotoxicity receptor co-ligands. Oncotarget 29 28969075
2019 Compound C620-0696, a new potent inhibitor targeting BPTF, the chromatin-remodeling factor in non-small-cell lung cancer. Frontiers of medicine 27 31104301
2016 BPTF Is Essential for T Cell Homeostasis and Function. Journal of immunology (Baltimore, Md. : 1950) 27 27799308
2016 BPTF Depletion Enhances T-cell-Mediated Antitumor Immunity. Cancer research 26 27651309
2021 Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies. American journal of medical genetics. Part A 25 33522091
2019 BPTF cooperates with p50 NF-κB to promote COX-2 expression and tumor cell growth in lung cancer. American journal of translational research 25 31934287
2018 NUP98-BPTF gene fusion identified in primary refractory acute megakaryoblastic leukemia of infancy. Genes, chromosomes & cancer 25 29427526
2019 Selectivity, ligand deconstruction, and cellular activity analysis of a BPTF bromodomain inhibitor. Organic & biomolecular chemistry 23 30706071
2021 Opportunity knocks for uncovering the new function of an understudied nucleosome remodeling complex member, the bromodomain PHD finger transcription factor, BPTF. Current opinion in chemical biology 22 33706239
2021 New Design Rules for Developing Potent Cell-Active Inhibitors of the Nucleosome Remodeling Factor (NURF) via BPTF Bromodomain Inhibition. Journal of medicinal chemistry 22 34515477
2021 Discovery of High-Affinity Inhibitors of the BPTF Bromodomain. Journal of medicinal chemistry 21 34375106
1996 Immunolocalization and redistribution of the FAC1 protein in Alzheimer's disease. Journal of neuropathology and experimental neurology 21 8786404
2017 Specific Acetylation Patterns of H2A.Z Form Transient Interactions with the BPTF Bromodomain. Biochemistry 19 28771339
2015 The Chromatin Remodeling Protein Bptf Promotes Posterior Neuroectodermal Fate by Enhancing Smad2-Activated wnt8a Expression. The Journal of neuroscience : the official journal of the Society for Neuroscience 19 26041917
2023 BPTF Drives Gastric Cancer Resistance to EGFR Inhibitor by Epigenetically Regulating the C-MYC/PLCG1/Perk Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 37863665
1997 FAC1 expression and localization in motor neurons of developing, adult, and amyotrophic lateral sclerosis spinal cord. Experimental neurology 17 9225734
2022 BPTF promotes the progression of distinct subtypes of breast cancer and is a therapeutic target. Frontiers in oncology 16 36530982
2020 New inhibitors for the BPTF bromodomain enabled by structural biology and biophysical assay development. Organic & biomolecular chemistry 16 32588860
2022 BPTF inhibition antagonizes colorectal cancer progression by transcriptionally inactivating Cdc25A. Redox biology 15 35932692
2020 hnRNPLL controls pluripotency exit of embryonic stem cells by modulating alternative splicing of Tbx3 and Bptf. The EMBO journal 15 33349972
2019 Discovery of alkoxy benzamide derivatives as novel BPTF bromodomain inhibitors via structure-based virtual screening. Bioorganic chemistry 14 30780018
1996 Identification and analysis of the complete cDNA sequence for the human FAC1 gene. Biochimica et biophysica acta 14 8950167
2018 MicroRNA-3666 inhibits lung cancer cell proliferation, migration, and invasiveness by targeting BPTF. Biochemistry and cell biology = Biochimie et biologie cellulaire 13 30481052
1999 DNA binding activity of the fetal Alz-50 clone 1 (FAC1) protein is enhanced by phosphorylation. Biochemical and biophysical research communications 13 10403843
2023 PHF6 recruits BPTF to promote HIF-dependent pathway and progression in YAP-high breast cancer. Journal of translational medicine 12 36967443
2022 circ-BPTF serves as a miR-486-5p sponge to regulate CEMIP and promotes hypoxic pulmonary arterial smooth muscle cell proliferation in COPD. Acta biochimica et biophysica Sinica 12 36514216
2021 Synthesis of NVS-BPTF-1 and evaluation of its biological activity. Bioorganic & medicinal chemistry letters 12 34146702
1998 The presence of FAC1 protein in Hirano bodies. Neuropathology and applied neurobiology 12 9821166
2022 Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR). Cancers 10 35326669
2021 N471D WASH complex subunit strumpellin knock-in mice display mild motor and cardiac abnormalities and BPTF and KLHL11 dysregulation in brain tissue. Neuropathology and applied neurobiology 10 34312900
1997 Expression of fetal ALZ-50 reactive clone 1 (FAC1) in dentate gyrus following entorhinal cortex lesion. The Journal of comparative neurology 10 9378851
2025 A BPTF-specific PROTAC degrader enhances NK cell-based cancer immunotherapy. Molecular therapy : the journal of the American Society of Gene Therapy 9 39935175
2023 Discovery of a Chemical Probe to Study Implications of BPTF Bromodomain Inhibition in Cellular and in vivo Experiments. ChemMedChem 8 36649575
2022 The effect of growth hormone treatment in children with novel BPTF gene variants: A report of two cases and literature review. Molecular genetics & genomic medicine 8 36153657
2020 Bptf determines oncogenic addiction in aggressive B-cell lymphomas. Oncogene 8 32451433
1987 Isolation and Characterization of Frankia sp. Strain FaC1 Genes Involved in Nitrogen Fixation. Applied and environmental microbiology 8 16347453
2022 NURF301 contributes to gypsy chromatin insulator-mediated nuclear organization. Nucleic acids research 7 35819192
2023 Discovery of new small molecule inhibitors of the BPTF bromodomain. Bioorganic chemistry 6 36898211
2023 The chromatin remodeling protein BPTF mediates cell cycle, proliferation and apoptosis in porcine ovarian granulosa cells. Theriogenology 6 37643502
2022 BPTF activates the MAPK pathway through coexpression with Raf1 to promote proliferation of T-cell lymphoma. Oncology letters 6 35720479
2003 Altered expression and distribution of FAC1 during NGF-induced neurite outgrowth of PC12 cells. Neuroreport 6 12634501
1998 Expression of FAC1 in activated microglia during Alzheimer's disease. Neuroscience letters 6 9792236
2024 Bromodomain inhibition targeting BPTF in the treatment of melanoma and other solid tumors. Clinical & experimental metastasis 5 38683257
2023 Genome-Wide Association Study of Chronic Dizziness in the Elderly Identifies Loci Implicating MLLT10, BPTF, LINC01224, and ROS1. Journal of the Association for Research in Otolaryngology : JARO 5 38036714
2022 Targeting regulation of VEGF by BPTF in non-small cell lung cancer and its potential clinical significance. European journal of medical research 5 36529788
2021 Discovery of selective BPTF bromodomain inhibitors by screening and structure-based optimization. Biochemical and biophysical research communications 5 33548625
2024 BPTF cooperates with MYCN and MYC to link neuroblastoma cell cycle control to epigenetic cellular states. bioRxiv : the preprint server for biology 4 38405949
2024 NUP98-BPTF promotes oncogenic transformation through PIM1 upregulation. Cancer medicine 4 38940430
2024 Lumbrokinase Extracted from Earthworms Synergizes with Bevacizumab and Chemotherapeutics in Treating Non-Small Cell Lung Cancer by Targeted Inactivation of BPTF/VEGF and NF-κB/COX-2 Signaling. Biomolecules 4 39062456
2023 BPTF in bone marrow provides a potential progression biomarker regulated by TFAP4 through the PI3K/AKT pathway in neuroblastoma. Biological procedures online 4 37170211
2023 Fragment-Based NMR Screening of the BPTF PHD Finger Methyl Lysine Reader Leads to the First Small-Molecule Inhibitors. ACS medicinal chemistry letters 4 37849548
2025 Chromatin remodeling protein BPTF mediates chromatin accessibility at gene promoters in planarian stem cells. BMC genomics 3 40069606
2024 Circ-Bptf Ameliorates Learning and Memory Impairments via the miR-138-5p/p62 Axis in APP/PS1 Mice. Molecular neurobiology 3 38528305
2024 Epilepsy as a Novel Phenotype of BPTF-Related Disorders. Pediatric neurology 3 38936258
2024 Chromatin remodeling protein BPTF regulates transcriptional stability in planarian stem cells. bioRxiv : the preprint server for biology 2 38826365
2025 Effects of the Missense Variants on Complete Phenotype and Splicing Variant on Severe Growth Retardation in the BPTF Gene. Developmental neurobiology 1 40415676
2025 BPTF Target Engagement by Acetylated H2A.Z Photoaffinity Probes. Biochemistry 1 40864556
2024 A role of BPTF in viral oncogenicity delineated through studies of heritable Kaposi sarcoma. Journal of medical virology 1 38380509
2024 Effect of bromodomain PHD-finger transcription factor (BPTF) on trophoblast epithelial-to-mesenchymal transition. Gene 1 38521110
2024 BPTF promotes glioma development through USP34-mediated de-ubiquitination of FOXC1. Histology and histopathology 1 38686761
2026 ENO2 and BPTF axis drives tumor progression and macrophage polarization in T2DM-associated colorectal cancer. Pathology, research and practice 0 41691935
2025 Cyclical Vomiting Syndrome in Individuals With BPTF Haploinsufficiency. Pediatric neurology 0 40614698
2025 Deciphering the molecular mechanisms of BPTF interactions with nucleosomes via molecular simulations. Biophysical journal 0 40616262
2025 Deciphering the Molecular Mechanisms of BPTF Interactions with Nucleosomes via Molecular Simulations. bioRxiv : the preprint server for biology 0 40661644
2025 Loss of BPTF restores estrogen response and suppresses metastasis of mammary tumors. Nature communications 0 41093864
2025 B/T Mixed Phenotype Acute Leukaemia Harbouring NUP98::BPTF Fusion. EJHaem 0 41098151
2025 BPTF-665aa mediate chromatin remodeling drives chemoresistance in T-LBL/ALL. Journal of experimental & clinical cancer research : CR 0 41204299
2025 BPTF regulates androgen receptor activity by enhancing chromatin accessibility and stabilizing the AR-FOXA1 interaction. Nature communications 0 41381516
2020 Correction: BPTF regulates growth of adult and pediatric high-grade glioma through the MYC pathway. Oncogene 0 31969682