| 2006 |
The PHD finger of BPTF (bromodomain-proximal PHD finger) specifically recognizes histone H3 trimethylated at K4 (H3K4me3) through anti-parallel beta-sheet formation, with the side chains of H3R2 and K4me3 fitting into adjacent pre-formed surface pockets flanking an invariant tryptophan. Crystal and NMR structures of free and H3K4me3-bound PHD finger established the molecular basis for site-specific readout; mutagenesis identified key specificity-determining residues. BPTF PHD shows preference for K4me3 over K4me2 and discriminates against monomethylated and unmodified H3. |
X-ray crystallography, NMR spectroscopy, peptide binding assays, PHD finger point mutagenesis |
Nature |
High |
16728978
|
| 2001 |
NURF301 (the Drosophila ortholog of BPTF) is the largest subunit of the NURF ISWI complex. Reconstitution of partial and full NURF complexes from recombinant proteins demonstrated that NURF301 and the ISWI ATPase are necessary and sufficient for accurate and efficient nucleosome sliding. An HMGA/HMGI(Y)-like domain of NURF301 facilitates sliding, indicating a role for DNA conformational changes. NURF301 also physically interacts with sequence-specific transcription factors, providing a basis for targeted recruitment. |
Recombinant protein reconstitution of NURF complexes, nucleosome sliding assays, protein interaction assays |
Molecular cell |
High |
11583616
|
| 2018 |
In the full nucleosomal context, histone H3 tails interact robustly and dynamically with nucleosomal DNA, substantially reducing BPTF PHD finger association with H3K4me3. Altering H3 tail electrostatics via modification or mutation increases PHD finger accessibility. This demonstrates that post-translational modification crosstalk can regulate BPTF PHD binding by modulating nucleosome conformation. |
NMR spectroscopy, molecular dynamics (MD) simulations, nucleosome binding assays with modified H3 tails |
eLife |
High |
29648537
|
| 2009 |
Drosophila NURF301 (BPTF ortholog) is expressed as alternative splice isoforms encoding functionally distinct NURF complexes. 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 NURF complex deficient in H3K4me3 and H4K16Ac recognition. Mutants lacking C-terminal PHD finger and bromodomain show a spermatocyte arrest phenotype and fail to express spermatid differentiation genes, revealing that the histone-modification-reading isoform is specifically required for spermatogenesis. |
Genetic analysis of Drosophila NURF301 isoform mutants, microarray expression profiling, phenotypic characterization |
PLoS genetics |
High |
19629165
|
| 2008 |
Bptf-null mouse embryos fail to establish a functional distal visceral endoderm and are reabsorbed by E8.5, establishing an essential role for BPTF in early embryogenesis. Physical and functional links between the BPTF-containing NURF complex and Smad transcription factors were identified, suggesting BPTF co-regulates TGF-β/Smad pathway targets required for visceral endoderm establishment. |
Bptf knockout mice, histological analysis, lineage marker immunostaining, microarray, co-immunoprecipitation with Smad factors |
PLoS genetics |
High |
18974875
|
| 2008 |
BPTF/FAC1 is essential in the extraembryonic trophoblast lineage for correct development of the ectoplacental cone; null embryos arrest at early gastrula stage (E6.5) with drastically reduced or absent ectoplacental cone, indicating BPTF is required for trophoblast differentiation. |
Loss-of-function allele knock-in mouse model, histological analysis, lineage marker staining |
Molecular and cellular biology |
High |
18794365
|
| 2015 |
BPTF physically interacts with the chromatin remodeling protein Bptf in zebrafish; Bptf functionally and physically interacts with phospho-Smad2 (activated by non-Nodal TGF-β signaling) to promote wnt8a expression required for neural posteriorization. Bptf and Smad2 directly bind to and activate the wnt8a promoter through recruiting the NURF remodeling complex. Knockdown of bptf increases nucleosome density at the wnt8a promoter. |
Zebrafish bptf morpholino knockdown, co-immunoprecipitation of Bptf and p-Smad2, ChIP at wnt8a promoter, nucleosome occupancy assay |
The Journal of neuroscience |
High |
26041917
|
| 2016 |
BPTF physically interacts with c-MYC and is required for full c-MYC transcriptional program activation. BPTF knockdown decreases c-MYC recruitment to DNA and reduces chromatin accessibility at c-MYC target loci. In Bptf-null MEFs, BPTF is necessary for c-MYC-driven proliferation, G1-S progression, and replication stress but not for c-MYC-driven apoptosis. Bptf inactivation in pre-neoplastic pancreatic acinar cells significantly delays tumor development in vivo. |
Co-immunoprecipitation (c-MYC and BPTF), ChIP (c-MYC at target genes), ATAC-seq/chromatin accessibility assays, Bptf-null MEFs, in vivo pancreatic cancer model |
Nature communications |
High |
26729287
|
| 2006 |
In C. elegans, the NURF301 ortholog NURF-1 acts together with ISWI (ISW-1) as a NURF-like complex to promote vulval cell fates and synMuv phenotype. isw-1 and nurf-1 mutations suppress the synMuv phenotype and the multivulva phenotype caused by Ras pathway overactivation, placing the NURF complex genetically downstream/parallel to Rb-like (lin-35) and Ras pathway in vulval fate determination. |
Genetic suppressor screen in C. elegans, double-mutant epistasis analysis |
Development |
Medium |
16774993
|
| 2000 |
FAC1 (alias of BPTF) protein interacts with the Myc-associated zinc finger protein ZF87/MAZ as shown by yeast two-hybrid and in vitro pulldown with recombinant protein. The interaction domain was mapped to the NLS/NES region of FAC1. FAC1 reduces ZF87/MAZ-induced transcriptional activation of the SV40 promoter in a dose-dependent manner in NIH3T3 cells; a FAC1 deletion mutant lacking the ZF87/MAZ interaction domain does not alter ZF87/MAZ activation. |
Yeast two-hybrid screen, in vitro pulldown with recombinant proteins, deletion mutagenesis, co-transfection luciferase reporter assay |
Biochemistry |
Medium |
10727212
|
| 1999 |
FAC1 (alias of BPTF) DNA-binding activity is regulated by phosphorylation: phosphatase treatment of neuroblastoma nuclear extracts reduces FAC1 DNA-binding affinity, and inhibition of cellular serine/threonine phosphatases increases FAC1 DNA-binding activity. |
Electrophoretic mobility shift assay (EMSA/DNA-binding assay), phosphatase treatment of nuclear extracts, pharmacological phosphatase inhibition |
Biochemical and biophysical research communications |
Medium |
10403843
|
| 2016 |
MITF directly binds the BPTF promoter (demonstrated by ChIP) and transcriptionally activates BPTF expression (demonstrated by luciferase reporter assay). MITF overexpression upregulates BPTF and BPTF-regulated genes including BCL2; MITF silencing downregulates BPTF. Rescue of MITF silencing-induced growth suppression by BPTF cDNA overexpression demonstrates BPTF transduces MITF-driven prosurvival signals. |
ChIP of MITF at BPTF promoter, luciferase reporter assay, shRNA silencing, BPTF cDNA rescue experiment |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
27185926
|
| 2017 |
BPTF occupies heparanase (HPSE) regulatory elements and activates its expression, as established using gain/loss-of-function approaches. Increased heparanase activity reduces cell-surface heparan sulfate proteoglycans (HSPGs), which are NCR co-ligands, thereby suppressing NK cell cytolytic activity toward tumor cells. Blocking NCR1 in vivo rescues BPTF-KD tumor weights, confirming the pathway. |
BPTF gain- and loss-of-function in syngeneic mouse models, HPSE promoter occupancy (implied ChIP), NK cell cytolytic assays, NCR1 blocking in vivo |
Oncotarget |
Medium |
28969075
|
| 2016 |
BPTF depletion in tumor cells enhances antigen processing by derepressing immunoproteasome subunits PSMB8 and PSMB9 and antigen transporter genes TAP1 and TAP2. ChIP/direct promoter occupancy experiments showed NURF directly regulates these gene loci. The PSMB8 inhibitor ONX-0914 reversed the enhanced CD8+ T-cell killing caused by BPTF ablation, confirming a role for the immunoproteasome. |
BPTF shRNA knockdown, ChIP of NURF at PSMB8/PSMB9/TAP1/TAP2 promoters, pharmacological epistasis with ONX-0914, CD8+ T-cell cytolytic assays |
Cancer research |
Medium |
27651309
|
| 2017 |
BPTF PHD finger preferentially binds H3K4me3 and recruits the NURF complex to chromatin, and depletion of BPTF reduces chromatin accessibility at enhancer regions in mammary epithelial cells. BPTF is essential for mammary gland stem cell (MaSC) self-renewal and differentiation; BPTF depletion arrests cells at a stage associated with an inability to achieve the luminal cell fate. |
BPTF KO/KD in mammary epithelial cells, ATAC-seq genome-wide chromatin accessibility, functional MaSC self-renewal assays |
Stem cell reports |
Medium |
28579392
|
| 2018 |
BPTF is required for the maintenance of hematopoietic stem/progenitor cell (HSPC) population size and long-term HSC function. Hematopoietic-specific knockout of Bptf causes bone marrow failure and anemia. Genome-wide transcriptome profiling showed BPTF loss causes downregulation of HSC stemness transcription factors (Meis1, Pbx1, Mn1, Lmo2) and BPTF potentiates chromatin accessibility of these genes. |
Conditional Bptf knockout mice, bone marrow transplantation reconstitution assay, RNA-seq, ATAC-seq at stemness gene loci |
Stem cell reports |
Medium |
29456179
|
| 2016 |
BPTF is critical for T cell homeostasis in a cell-intrinsic manner. Treg cell-specific BPTF deletion leads to reduced Foxp3 expression, increased lymphocyte infiltration in non-lymphoid organs, and a systemic autoimmune syndrome. |
Conditional Bptf knockout from late DN3/DN4 T cells, Treg-specific Bptf deletion, flow cytometry, histological analysis of organ infiltration |
Journal of immunology |
Medium |
27799308
|
| 2019 |
BPTF cooperates with p50 subunit of NF-κB to regulate COX-2 promoter activity and COX-2 expression in lung cancer cells. BPTF was identified as a COX-2 promoter-binding protein; knockdown of BPTF abrogated p50 binding to the COX-2 promoter; inhibition of p50 activity blocked BPTF-dependent COX-2 expression and cell proliferation. |
Biotin-streptavidin-agarose DNA pulldown of COX-2 promoter, mass spectrometry identification, ChIP, co-immunoprecipitation of BPTF and p50, confocal immunofluorescence, BPTF siRNA knockdown |
American journal of translational research |
Medium |
31934287
|
| 2018 |
BPTF promotes HCC growth by transcriptionally regulating hTERT expression. Knockdown of BPTF suppressed hTERT expression, reduced cancer stem cell marker expression, and inhibited tumor growth in xenograft models. |
BPTF shRNA knockdown, ChIP (implied for BPTF at hTERT promoter), xenograft mouse model, Western blot for CSC markers |
Redox biology |
Low |
30419422
|
| 2015 |
The BPTF bromodomain was identified as a druggable target; AU1 was identified as the first small molecule selective for BPTF bromodomain over Brd4 (Kd = 2.8 μM by 19F NMR). No binding was detected with Brd4. AU1 is active in a cell-based reporter assay. |
Protein-observed 19F NMR dual screening, fluorescence anisotropy, cell-based reporter assay |
ACS chemical biology |
Medium |
26158404
|
| 2017 |
H2A.Z diacetylated at K4 and K11 directly interacts with the BPTF bromodomain with Kd ~780 μM, as established by PrOF NMR and photo-cross-linking. Specificity for the K4/K11 diacetylation pattern over other combinations was demonstrated biophysically. |
Protein-observed 19F NMR (PrOF NMR), 1H NMR CPMG experiments, photo-cross-linking, fluorescence anisotropy |
Biochemistry |
Medium |
28771339
|
| 2022 |
BPTF binds the Cdc25A promoter (−178/+107 region) and transcriptionally activates Cdc25A to accelerate colorectal cancer cell cycle progression. BPTF itself is transcriptionally regulated by c-Myc. Established by RNA-seq, DNA-pulldown, ChIP, and luciferase reporter assay; Cdc25A overexpression partially reversed BPTF-silencing-induced growth inhibition (epistasis). |
RNA-seq, DNA pulldown, ChIP at Cdc25A promoter, luciferase reporter assay, siRNA/shRNA knockdown, rescue with Cdc25A overexpression |
Redox biology |
Medium |
35932692
|
| 2022 |
BPTF is required for c-MYC recruitment to the promoter of ABC-transporters (MDR genes) in pancreatic cancer. BPTF silencing reduces IC50 of gemcitabine in vitro, and its depletion increases intracellular gemcitabine accumulation and DNA damage. ChIP confirmed reduced c-MYC occupancy at ABC-transporter promoters upon BPTF knockdown. |
BPTF siRNA/shRNA knockdown, ChIP (c-MYC at ABC-transporter promoters), gemcitabine sensitivity assays, DNA damage assays, xenograft models |
Cancers |
Medium |
35326669
|
| 2020 |
Bptf deletion in aggressive B-cell lymphoma (Eμ-Myc mouse model) delays lymphomagenesis; tumors arising in a Bptf heterozygous background display decreased c-MYC levels, reduced c-MYC pathway activity, and increased NF-κB pathway activation. This defines BPTF as genetically required for c-MYC-driven B-cell lymphomagenesis. |
Eμ-Myc transgenic mouse with Bptf heterozygous deletion, tumor analysis, gene expression profiling, IHC for c-MYC/NF-κB pathway |
Oncogene |
Medium |
32451433
|
| 2025 |
BPTF forms a protein complex with androgen receptor (AR) and FOXA1 in prostate cancer. BPTF increases chromatin accessibility via SMARCA1 (catalytic NURF subunit) to facilitate AR binding at promoters, enhancers, and super-enhancers. FOXA1 recruits the BPTF-AR complex to chromatin, while BPTF stabilizes the AR-FOXA1 interaction. BPTF interacts with AR through its bromodomain; a bromodomain inhibitor disrupts this interaction and impairs AR signaling. |
Co-immunoprecipitation (BPTF, AR, FOXA1), ChIP-seq (BPTF, AR), ATAC-seq (chromatin accessibility), RNA-seq, BPTF bromodomain inhibitor treatment |
Nature communications |
High |
41381516
|
| 2025 |
BPTF PHD finger reads H3K4me3 to protect hepatocellular carcinoma (HCC) cells from NK cell recognition. PROTAC-mediated selective degradation of BPTF directly increases the abundance of natural cytotoxicity receptor ligands on HCC cells, enhancing NK cell cytotoxicity against HCC both in vitro and in vivo. |
PROTAC degrader, NK cell cytotoxicity assays, surface NCR ligand analysis, in vivo HCC models |
Molecular therapy |
Medium |
39935175
|
| 2025 |
BPTF bromodomain directly binds acetylated H2A.Z in a pocket-specific and affinity-dependent manner in vitro (photo-crosslinking with recombinant bromodomain) and enriches endogenous BPTF from nuclear lysates of A549 cells, confirming the interaction occurs in a cellular context, albeit less efficiently than with canonical H4K16ac. |
Photoaffinity probes with diazirine and biotin tag, SDS-PAGE photo-crosslinking, nuclear lysate pull-down, bottom-up proteomics for H2A.Z acetylation patterns |
Biochemistry |
Medium |
40864556
|
| 2024 |
BPTF cooperates with MYCN and MYC in neuroblastoma; immunoprecipitation/mass spectrometry showed BPTF interacts with MYCN and core regulatory circuitry (CRC) transcription factors. Genome-wide distribution analysis revealed BPTF co-localizes with MYCN/MYC at promoters of cell cycle genes and with CRC factors at super-enhancers to regulate cell identity. |
Immunoprecipitation/mass spectrometry, ChIP-seq (BPTF, MYCN, CRC TFs), bulk RNA-seq, single-cell sequencing, tissue microarrays |
bioRxivpreprint |
Medium |
38405949
|
| 2024 |
NUP98-BPTF fusion protein promotes oncogenic transformation by transcriptionally upregulating PIM1 proto-oncogene via binding to its promoter, leading to activation of MYC and mTORC1 signaling. PIM1 knockdown or mTORC1 inhibition suppressed NUP98-BPTF-induced NIH3T3 transformation. NUP98-BPTF also inactivates the pro-apoptotic protein BAD to enhance leukemia cell survival. |
Doxycycline-inducible NUP98-BPTF expression, NIH3T3 transformation assay, ChIP at PIM1 promoter, PIM1 shRNA knockdown, pharmacological mTORC1 inhibition, Jurkat T-ALL survival assays |
Cancer medicine |
Medium |
38940430
|
| 2025 |
BPTF regulates trophoblast EMT by directly binding the Slug gene promoter and activating Slug transcription. BPTF knockdown prevented EMT and attenuated trophoblast invasion; Slug and BPTF protein levels were both decreased in villous cytotrophoblasts of recurrent miscarriage patients. |
ChIP (BPTF at Slug promoter), BPTF knockdown, EMT assays, invasion assays, immunostaining of patient villi |
Gene |
Low |
38521110
|
| 2022 |
NURF301 (Drosophila BPTF ortholog) co-localizes genome-wide with gypsy insulator proteins CP190 and Su(Hw) and promotes chromatin association of these insulator proteins at gypsy insulator binding sites, as shown by ChIP-seq. NURF301 physically interacts with gypsy insulator proteins and promotes nucleosome repositioning at insulator sites, contributing to 3D nuclear organization of gypsy insulator binding sites. |
RNAi screen, ChIP-seq (NURF301, Su(Hw), CP190), physical interaction assays (pulldown/IP with insulator proteins), Oligopaint FISH with immunofluorescence for 3D localization, nucleosome positioning assay |
Nucleic acids research |
Medium |
35819192
|
| 2021 |
METTL14-mediated m6A modification negatively regulates BPTF mRNA stability, such that METTL14 deficiency leads to BPTF accumulation. Accumulated BPTF remodels the enhancer landscape in renal cell carcinoma, constituting super-enhancers that activate downstream oncogenic targets including ENO2 and SRC, leading to glycolytic reprogramming. |
MeRIP-seq, RNA-seq, ChIP-seq, ATAC-seq, BPTF knockdown, METTL14 knockout, organoid and xenograft models, BPTF inhibitor AU1 treatment |
Theranostics |
Medium |
33664855
|
| 2025 |
Loss of BPTF in mammary tumors results in elevated ERα levels linked with decreased TGF-β activity, leading to tamoxifen-sensitive estrogen-responsive tumors with limited lung metastasis. Loss of ERα is sufficient to restore TGF-β activity and metastatic potential in BPTF-KO tumors, establishing an epistatic relationship between BPTF, TGF-β, and ERα in tumor progression. |
Conditional BPTF knockout mammary tumor model, ERα/TGF-β functional analysis, ERα loss-of-function rescue experiment, lung metastasis assay |
Nature communications |
Medium |
41093864
|
| 2025 |
BPTF operates at gene promoters and is most effective at facilitating transcription and chromatin accessibility at genes marked by Set1-dependent H3K4me3 peaks (broader peaks) but not MLL1/2-dependent H3K4me3. Loss-of-function phenotype of bptf knockdown in planarian stem cells mimics that of Set1 knockdown, establishing a functional epistatic relationship between BPTF and Set1-H3K4me3 in vivo. |
BPTF RNAi knockdown in planarian stem cells, ATAC-seq, RNA-seq, Set1 vs MLL1/2 ChIP-seq peak comparison, genetic epistasis (bptf vs set1 knockdown phenotype) |
BMC genomics |
Medium |
40069606
|
| 2025 |
Molecular dynamics simulations show that BPTF PHD finger binding to H3K4me3 displaces the H3 tail from nucleosomal DNA, increasing H3 tail flexibility and promoting compensatory binding of the H4 tail to nucleosomal DNA. This redistribution weakens overall DNA-histone hydrogen bonding, suggesting BPTF engagement induces localized nucleosome destabilization. BPTF adopts a compacted conformation upon nucleosome engagement. |
Molecular dynamics simulations of BPTF PHD finger and bromodomain bound to H3 peptide or full nucleosome |
Biophysical journal |
Low |
40616262
|
| 2021 |
Cocrystal structures of the BPTF bromodomain with small molecule inhibitors (BZ1 series pyridazinones) were determined, identifying an acidic triad in the binding pocket that guides inhibitor design. BZ1 showed Kd = 6.3 nM and >350-fold selectivity over BET bromodomains. |
X-ray co-crystallography of BPTF bromodomain:inhibitor complexes, ITC, SPR binding assays |
Journal of medicinal chemistry |
High |
34515477
|
| 2021 |
Cocrystal structures of the BPTF bromodomain with small molecule inhibitors DC-BPi-07 and DC-BPi-11 were determined, demonstrating the rational basis for high-affinity (>100-fold selective over other BRD targets) inhibition at the atomic level. |
X-ray cocrystallography, biochemical IC50 assays, selectivity profiling |
Journal of medicinal chemistry |
High |
34375106
|
| 2020 |
First published cocrystal structures of the BPTF bromodomain with small molecule inhibitors were reported, providing structural validation for ligand binding modes and guiding medicinal chemistry. |
X-ray crystallography of BPTF bromodomain:ligand complexes, PrOF NMR, SPR, AlphaScreen |
Organic & biomolecular chemistry |
High |
32588860
|
| 2025 |
Nucleosome Mass Spectrometry (Nuc-MS) directly revealed that the BPTF PHD-bromodomain tandem reader requires coincident H3K4me3, K9ac, K14ac, and K18ac for effective nucleosome engagement, demonstrating that multivalent combinatorial histone PTM reading is required for productive BPTF-nucleosome interaction. |
Native top-down nucleosome mass spectrometry (Nuc-MS) disassembly of CAP:nucleosome complexes, histone proteoform identification |
bioRxivpreprint |
Medium |
bio_10.1101_2025.05.01.651740
|