{"gene":"DPF2","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2024,"finding":"DPF2 binds H3K14 lactylation (H3K14la) via its PHD finger domain, co-localizes with H3K14la on promoters of oncogenic genes, and this interaction drives oncogenic gene transcription; structure-guided mutagenesis disrupting the DPF2-H3K14la interaction blunts cancer-related gene expression and cell survival.","method":"Multivalent photoaffinity probe with quantitative proteomics, biochemical binding assays, CUT&Tag chromatin mapping, structure-guided mutagenesis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (photoaffinity proteomics, biochemical assays, CUT&Tag, mutagenesis) in a single rigorous study establishing DPF2 as a bona fide H3K14la reader","pmids":["39636855"],"is_preprint":false},{"year":2017,"finding":"The tandem PHD finger domain of DPF2 directly binds acetylated tails of both histone H3 and H4 via bipartite binding pockets on the DPF2 surface; targeted mutagenesis of these pockets abolishes DPF2 recruitment to target chromatin and its ability to prevent myeloid differentiation in vivo.","method":"Crystal structure at 1.6-Å resolution, histone peptide binding assays, targeted mutagenesis, chromatin recruitment assays, in vivo myeloid differentiation assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with mutagenesis validated by functional in vivo assay, multiple orthogonal methods in one rigorous study","pmids":["28533407"],"is_preprint":false},{"year":2024,"finding":"DPF2 PHD1 domain binds crotonylated H3K14 (H3K14Cr) through both PHD1 and PHD2 pockets as defined by protein footprinting mass spectrometry; this interaction is preserved when BAF45D is within the intact BAF complex, and the ATPase BRM also displays H3K14Cr-protected peptides in two domains.","method":"Protein footprinting mass spectrometry (hydroxyl radical footprinting), binding assays with isolated DPF domain and full BAF complex","journal":"ACS bio & med chem Au","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — novel footprinting MS method with orthogonal binding assays, single lab, no prior replication of this specific finding","pmids":["39184054"],"is_preprint":false},{"year":2011,"finding":"The C2H2-type zinc finger domain of DPF2 adopts a canonical C2H2 fold with two beta strands and one alpha helix; conserved residues Lys207, Lys216, and Arg217 form a positively charged surface implicating potential DNA-binding capacity.","method":"X-ray crystal structure determination","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — crystal structure established, but DNA-binding capacity is inferred structurally and not experimentally validated in this paper","pmids":["21888896"],"is_preprint":false},{"year":2010,"finding":"DPF2 acts as a co-repressor for ERRα by directly binding ERRα, recognizing acetylated histone H3, and associating with HDAC1; DPF2 is recruited to ERR target gene promoters in myoblast cells and its knockdown derepresses ERRα target gene mRNA levels.","method":"Biochemical purification from HeLa cells, co-immunoprecipitation, GST pulldown, ChIP, siRNA knockdown with gene expression analysis","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal biochemical assays plus ChIP plus functional knockdown in a single lab with multiple orthogonal methods","pmids":["20400511"],"is_preprint":false},{"year":2015,"finding":"DPF2 directly interacts with OCT4 protein, promotes its poly-ubiquitination via K48-linked ubiquitin chains, and targets it for proteasomal degradation; DPF2 PHD2 domain is required for ubiquitination activity but both wild-type and PHD2 mutant DPF2 redistribute nuclear OCT4.","method":"Co-immunoprecipitation, GST pulldown, in vitro ubiquitination assay, siRNA knockdown, overexpression in 293 cells","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro ubiquitination assay plus multiple cell-based assays (Co-IP, GST pulldown, KD/OE) in single lab","pmids":["26417682"],"is_preprint":false},{"year":2019,"finding":"Dpf2 co-occupies enhancers with Oct4, Sox2, p300, and Brg1 in ESCs; deletion of Dpf2 represses Tbx3 through loss of H3K27ac at its distal enhancer and impairs mesendodermal differentiation, which can be rescued by restoring Tbx3 expression. PRC2 subunit Eed antagonizes Dpf2-dependent Tbx3 expression by binding an intragenic Tbx3 enhancer.","method":"ChIP-seq, ATAC-seq, genetic deletion (Dpf2 KO ESCs), rescue experiments (Tbx3 re-expression), genetic epistasis (Dpf2 vs. Eed/Ezh2)","journal":"Cell stem cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with rescue, epistasis analysis, and multiple chromatin profiling methods establishing pathway position and mechanism","pmids":["30609396"],"is_preprint":false},{"year":2018,"finding":"Missense variants in DPF2 PHD1 and PHD2 domains found in Coffin-Siris syndrome abolish or impair DPF2 binding to unmodified and modified H3 histone tails; overexpression of these variants causes formation of nuclear aggregates that recruit wild-type DPF2 and BRG1, consistent with a dominant-negative mechanism.","method":"Pull-down assays with recombinant proteins and histone peptides, overexpression in HEK293 and COS7 cells, immunofluorescence","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding assays with disease mutations plus cell-based dominant-negative evidence, single lab","pmids":["29429572"],"is_preprint":false},{"year":2017,"finding":"DPF2 functions in the non-canonical NF-κB pathway to suppress type I interferon (IFN-β) induction; knockdown of DPF2 in influenza-infected cells increases IFN-β expression, phosphorylation of STAT1, and production of antiviral proteins, while reducing viral protein expression and progeny virus by ~2 logs.","method":"RNAi screen (2,732 genes), siRNA knockdown, viral growth kinetics assay, IFN-β/cytokine measurement, Western blot for STAT1 phosphorylation","journal":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional KD with defined signaling readouts (IFN-β, STAT1), multiple assays, single lab","pmids":["28404846"],"is_preprint":false},{"year":2025,"finding":"Loss of Dpf2 in macrophages reduces H3K27ac and H3K4me1 marks at the Cacna1d enhancer, impairing Cacna1d mRNA expression and reducing intracellular calcium; this attenuates MAPK signaling and promotes anti-inflammatory macrophage polarization, protecting against intestinal injury.","method":"Mouse genetic knockout, single-cell RNA sequencing, spatial transcriptomics, ChIP for histone marks, MAPK signaling assays, patient-derived organoids","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — mouse genetics with mechanistic dissection through chromatin marks, downstream signaling, and validation in human clinical samples using multiple orthogonal methods","pmids":["41223220"],"is_preprint":false},{"year":2018,"finding":"BAF45d (DPF2) alternative splicing is regulated by PTBP1 (polypyrimidine tract-binding protein 1), and reciprocally, BAF45d regulates PTBP1 splicing activity, establishing a feedback loop between RNA splicing regulation and transcription in glioblastoma.","method":"Splicing array, mechanistic and functional studies in glioblastoma patient samples and cell lines, siRNA/overexpression experiments","journal":"Neuro-oncology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — reciprocal regulation demonstrated with functional assays, but abstract lacks detail on specific biochemical methods for the PTBP1–DPF2 interaction","pmids":["29373718"],"is_preprint":false},{"year":2015,"finding":"DPF2 (along with SMARCA4/BRG1 and SMARCD2/BAF60B) is selectively required for leukaemic cell expansion and self-renewal in MLL-rearranged leukaemia; gene expression profiling shows these subunits have overlapping functions in maintaining haematopoietic stem cell-associated gene expression but are not required for c-MYC target gene expression in human cells.","method":"shRNA knockdown, gene expression profiling, in vitro and in vivo leukaemia models","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined transcriptional phenotype, but DPF2-specific mechanism partially conflated with two other subunits","pmids":["26571505"],"is_preprint":false},{"year":2024,"finding":"In H9-derived spinal cord neural stem cells (NSCs), BAF45D (DPF2) preferentially binds anterior and trunk/central HOX gene loci and the NES gene, with markedly greater chromatin enrichment compared to ESCs, and also targets TBX6, a regulator of spinal cord neural mesodermal progenitors.","method":"ChIP-seq (CUT&RUN or similar chromatin binding assay) comparing ESC vs. spinal cord NSC chromatin","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — chromatin binding data without functional perturbation experiments establishing causal role, single lab","pmids":["38168763"],"is_preprint":false}],"current_model":"DPF2 (BAF45d) is a histone-reader subunit of the BAF (SWI/SNF) chromatin-remodeling complex whose tandem PHD finger domain directly binds acetylated, crotonylated, and lactylated histone H3/H4 tails to recruit or stabilize the BAF complex at enhancers and promoters; through this chromatin-reading activity DPF2 regulates transcriptional programs controlling myeloid differentiation, ESC pluripotency/differentiation (antagonizing PRC2 at Tbx3), macrophage inflammatory polarization via CACNA1D-MAPK signaling, and oncogene expression, while also acting as an E3-like ubiquitin ligase that targets OCT4 for K48-linked proteasomal degradation and functioning in the non-canonical NF-κB pathway to suppress innate interferon responses."},"narrative":{"mechanistic_narrative":"DPF2 (BAF45d) is a histone-reader subunit of the BAF (SWI/SNF) chromatin-remodeling complex that couples recognition of modified histone tails to the regulation of cell-type-specific transcriptional programs [PMID:28533407, PMID:30609396]. Its tandem PHD finger module directly binds acetylated histone H3 and H4 tails through bipartite binding pockets, and structure-guided mutation of these pockets abolishes DPF2 chromatin recruitment and its ability to block myeloid differentiation [PMID:28533407]. This reader activity extends beyond acetylation to other acyl marks: DPF2 engages crotonylated H3K14 through its PHD1/PHD2 pockets while embedded in the intact BAF complex [PMID:39184054], and binds H3K14 lactylation to drive transcription of oncogenic genes, where disrupting the DPF2–H3K14la interaction blunts cancer-gene expression and cell survival [PMID:39636855]. In embryonic stem cells DPF2 co-occupies enhancers with OCT4, SOX2, p300, and BRG1, and is required for Tbx3 expression via H3K27ac at its distal enhancer, antagonizing the PRC2 subunit EED to enable mesendodermal differentiation [PMID:30609396]; an analogous enhancer-licensing role operates in macrophages, where DPF2 sustains H3K27ac/H3K4me1 at the Cacna1d enhancer to promote calcium-dependent MAPK signaling and inflammatory polarization [PMID:41223220]. DPF2 also acts as a transcriptional co-repressor for ERRα in association with HDAC1 [PMID:20400511], promotes K48-linked polyubiquitination and proteasomal degradation of OCT4 in a manner requiring its PHD2 domain [PMID:26417682], and functions in the non-canonical NF-κB pathway to suppress type I interferon induction during influenza infection [PMID:28404846]. Heterozygous missense variants in the PHD1/PHD2 domains cause Coffin-Siris syndrome, impairing histone-tail binding and acting through a dominant-negative mechanism that sequesters wild-type DPF2 and BRG1 [PMID:29429572].","teleology":[{"year":2010,"claim":"Established that DPF2 is not merely a structural subunit but a transcriptional regulator, acting as a co-repressor that links a nuclear receptor to histone deacetylase activity.","evidence":"Biochemical purification, Co-IP/GST pulldown, ChIP, and siRNA knockdown in myoblasts","pmids":["20400511"],"confidence":"Medium","gaps":["Did not resolve whether repression depends on PHD-domain histone reading versus HDAC1 recruitment","Generality beyond ERRα targets untested"]},{"year":2011,"claim":"Defined the structure of the DPF2 C2H2 zinc finger, raising the possibility of a DNA-contacting surface in addition to histone reading.","evidence":"X-ray crystal structure of the C2H2 domain","pmids":["21888896"],"confidence":"Medium","gaps":["DNA-binding capacity inferred from surface charge only, not experimentally validated","Functional relevance of the proposed DNA contacts unknown"]},{"year":2015,"claim":"Revealed a non-chromatin enzymatic role: DPF2 directs K48-linked ubiquitination and proteasomal degradation of the pluripotency factor OCT4, connecting it to control of the pluripotency network.","evidence":"Co-IP, GST pulldown, in vitro ubiquitination, knockdown/overexpression in 293 cells","pmids":["26417682"],"confidence":"Medium","gaps":["Whether DPF2 is the direct E3 ligase or a recruiting adaptor not resolved","PHD2 requirement for ubiquitination mechanistically unexplained"]},{"year":2015,"claim":"Placed DPF2 within a functionally required BAF subunit set for MLL-rearranged leukaemia, framing it as a dependency in oncogenic transcriptional maintenance.","evidence":"shRNA knockdown with gene expression profiling and in vitro/in vivo leukaemia models","pmids":["26571505"],"confidence":"Medium","gaps":["DPF2-specific contribution partially conflated with SMARCA4 and SMARCD2","Direct target genes of DPF2 in this context not isolated"]},{"year":2017,"claim":"Provided the structural basis for DPF2 as a dual-acetyl reader, showing the tandem PHD module binds acetylated H3 and H4 tails and that this reading is functionally required to block myeloid differentiation.","evidence":"1.6-Å crystal structure, histone peptide binding, targeted mutagenesis, in vivo myeloid differentiation assay","pmids":["28533407"],"confidence":"High","gaps":["Did not address acyl marks beyond acetylation","Did not map genome-wide targets controlled by this reading activity"]},{"year":2017,"claim":"Identified a signaling role beyond chromatin, showing DPF2 in the non-canonical NF-κB pathway restrains type I interferon antiviral responses.","evidence":"RNAi screen, siRNA knockdown, viral growth kinetics, IFN-β/STAT1 readouts in influenza-infected cells","pmids":["28404846"],"confidence":"Medium","gaps":["Molecular link between DPF2 and NF-κB components undefined","Unclear whether this requires BAF complex or histone-reading activity"]},{"year":2018,"claim":"Established DPF2 as a Coffin-Siris syndrome gene and connected disease variants mechanistically to loss of histone-tail binding and dominant-negative sequestration of BAF.","evidence":"Recombinant pull-down with histone peptides, overexpression and immunofluorescence in HEK293/COS7","pmids":["29429572"],"confidence":"Medium","gaps":["Dominant-negative aggregate behavior shown by overexpression, not endogenous variants","Tissue-specific developmental consequences not modeled"]},{"year":2018,"claim":"Linked DPF2 to an RNA-splicing feedback loop with PTBP1, expanding its regulatory reach from transcription into splicing in glioblastoma.","evidence":"Splicing array and functional siRNA/overexpression studies in glioblastoma samples and cell lines","pmids":["29373718"],"confidence":"Medium","gaps":["Biochemical basis of the DPF2–PTBP1 interaction not detailed","Direct versus indirect reciprocal regulation unresolved"]},{"year":2019,"claim":"Positioned DPF2 in the ESC enhancer network, showing it co-occupies pluripotency enhancers and licenses Tbx3 expression by antagonizing PRC2 to enable mesendodermal differentiation.","evidence":"ChIP-seq, ATAC-seq, Dpf2 KO ESCs with Tbx3 rescue and Dpf2/Eed epistasis","pmids":["30609396"],"confidence":"High","gaps":["How DPF2 reading translates into H3K27ac deposition at the enhancer not fully resolved","Mechanism of antagonism with EED at the intragenic enhancer not detailed"]},{"year":2024,"claim":"Extended DPF2 reading specificity to crotonylation, demonstrating PHD-mediated engagement of H3K14Cr is preserved within the assembled BAF complex.","evidence":"Hydroxyl radical protein footprinting MS with binding assays on isolated DPF domain and full BAF complex","pmids":["39184054"],"confidence":"Medium","gaps":["Functional/transcriptional consequence of H3K14Cr reading not tested","Single-lab footprinting method not independently replicated"]},{"year":2024,"claim":"Defined DPF2 as a histone lactylation reader and tied this directly to oncogenic transcription, showing disruption of the H3K14la interaction impairs cancer-gene expression and cell survival.","evidence":"Photoaffinity proteomics, biochemical binding, CUT&Tag, structure-guided mutagenesis","pmids":["39636855"],"confidence":"High","gaps":["Identity of the full oncogenic gene set governed by H3K14la reading incomplete","In vivo tumor dependence not established"]},{"year":2024,"claim":"Mapped a developmental-stage shift in DPF2 chromatin targeting, showing preferential binding of anterior/trunk HOX loci, NES, and TBX6 in spinal cord neural stem cells.","evidence":"Chromatin binding profiling (CUT&RUN-type) comparing ESCs and spinal cord NSCs","pmids":["38168763"],"confidence":"Low","gaps":["Descriptive binding data without functional perturbation establishing causal role","Single lab, no rescue or knockout validation"]},{"year":2025,"claim":"Demonstrated an in vivo enhancer-licensing role in immune cells, where DPF2 sustains Cacna1d enhancer marks to drive calcium-dependent MAPK signaling and inflammatory macrophage polarization.","evidence":"Mouse KO, scRNA-seq, spatial transcriptomics, ChIP for histone marks, MAPK assays, patient organoids","pmids":["41223220"],"confidence":"High","gaps":["Direct DPF2 reading of a specific acyl mark at the Cacna1d enhancer not pinpointed","Whether MAPK attenuation is solely Cacna1d-dependent untested"]},{"year":null,"claim":"How DPF2's distinct activities — multivalent histone acyl reading, BAF recruitment, ERRα co-repression, OCT4 ubiquitination, and NF-κB signaling — are integrated and switched between contexts remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No unifying model linking chromatin-reading to the ubiquitin-ligase activity","Determinants of cell-type-specific target selection (HOX vs. enhancers vs. oncogenes) unknown","Whether NF-κB and splicing roles depend on BAF complex membership untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[0,1,2,7]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[4,6]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[5]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[5,7]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0,1,6]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,1,6]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[4,6,9]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[6,12]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[8,9]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[7]}],"complexes":["BAF (SWI/SNF) complex"],"partners":["SMARCA4","OCT4","ESRRA","HDAC1","SOX2","EP300","EED","PTBP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q92785","full_name":"Zinc finger protein ubi-d4","aliases":["Apoptosis response zinc finger protein","BRG1-associated factor 45D","BAF45D","D4, zinc and double PHD fingers family 2","Protein requiem"],"length_aa":391,"mass_kda":44.2,"function":"Plays an active role in transcriptional regulation by binding modified histones H3 and H4 (PubMed:27775714, PubMed:28533407). Is a negative regulator of myeloid differentiation of hematopoietic progenitor cells (PubMed:28533407). Might also have a role in the development and maturation of lymphoid cells (By similarity). Involved in the regulation of non-canonical NF-kappa-B pathway (PubMed:20460684)","subcellular_location":"Nucleus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q92785/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DPF2","classification":"Not Classified","n_dependent_lines":461,"n_total_lines":1208,"dependency_fraction":0.38162251655629137},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"ARID1A","stoichiometry":10.0},{"gene":"SMARCB1","stoichiometry":10.0},{"gene":"SMARCC1","stoichiometry":10.0},{"gene":"SMARCC2","stoichiometry":10.0},{"gene":"SMARCD1","stoichiometry":10.0},{"gene":"SMARCD2","stoichiometry":10.0},{"gene":"SMARCE1","stoichiometry":10.0},{"gene":"ARID1B","stoichiometry":4.0},{"gene":"SMARCA4","stoichiometry":4.0},{"gene":"ACTB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/DPF2","total_profiled":1310},"omim":[{"mim_id":"618027","title":"COFFIN-SIRIS SYNDROME 7; CSS7","url":"https://www.omim.org/entry/618027"},{"mim_id":"601671","title":"D4, ZINC, AND DOUBLE PHD FINGERS FAMILY, MEMBER 2; DPF2","url":"https://www.omim.org/entry/601671"},{"mim_id":"135900","title":"COFFIN-SIRIS SYNDROME 1; CSS1","url":"https://www.omim.org/entry/135900"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Vesicles","reliability":"Additional"},{"location":"Centrosome","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DPF2"},"hgnc":{"alias_symbol":["ubi-d4","BAF45d","SMARCG2"],"prev_symbol":["REQ"]},"alphafold":{"accession":"Q92785","domains":[{"cath_id":"3.30.40.10","chopping":"309-386","consensus_level":"high","plddt":95.2729,"start":309,"end":386}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92785","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q92785-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q92785-F1-predicted_aligned_error_v6.png","plddt_mean":69.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DPF2","jax_strain_url":"https://www.jax.org/strain/search?query=DPF2"},"sequence":{"accession":"Q92785","fasta_url":"https://rest.uniprot.org/uniprotkb/Q92785.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q92785/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92785"}},"corpus_meta":[{"pmid":"39636855","id":"PMC_39636855","title":"DPF2 reads histone lactylation to drive transcription and tumorigenesis.","date":"2024","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/39636855","citation_count":78,"is_preprint":false},{"pmid":"29429572","id":"PMC_29429572","title":"Mutations in the BAF-Complex Subunit DPF2 Are Associated with Coffin-Siris Syndrome.","date":"2018","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/29429572","citation_count":71,"is_preprint":false},{"pmid":"30609396","id":"PMC_30609396","title":"The BAF and PRC2 Complex Subunits Dpf2 and Eed Antagonistically Converge on Tbx3 to Control ESC Differentiation.","date":"2019","source":"Cell stem cell","url":"https://pubmed.ncbi.nlm.nih.gov/30609396","citation_count":39,"is_preprint":false},{"pmid":"28533407","id":"PMC_28533407","title":"Histone-binding of DPF2 mediates its repressive role in myeloid differentiation.","date":"2017","source":"Proceedings 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OCT4 protein level and nuclear distribution.","date":"2015","source":"Data in brief","url":"https://pubmed.ncbi.nlm.nih.gov/26958616","citation_count":3,"is_preprint":false},{"pmid":"39184054","id":"PMC_39184054","title":"Mass Spectrometry-Based Protein Footprinting Defines the Binding Pocket of Crotonylated H3K14 in the PHD1 Domain of BAF45D within the BAF Chromatin Remodeling Complex.","date":"2024","source":"ACS bio & med chem Au","url":"https://pubmed.ncbi.nlm.nih.gov/39184054","citation_count":2,"is_preprint":false},{"pmid":"38168763","id":"PMC_38168763","title":"BAF45D-binding to HOX genes was differentially targeted in H9-derived spinal cord neural stem cells.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38168763","citation_count":1,"is_preprint":false},{"pmid":"42232179","id":"PMC_42232179","title":"The crotonylation reader DPF2 promotes the development and progression of colon adenocarcinoma through cell-type-specific immune regulation and metabolic reprogramming.","date":"2026","source":"Frontiers in pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/42232179","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11054,"output_tokens":3350,"usd":0.041706,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10873,"output_tokens":4422,"usd":0.082458,"stage2_stop_reason":"end_turn"},"total_usd":0.124164,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"DPF2 binds H3K14 lactylation (H3K14la) via its PHD finger domain, co-localizes with H3K14la on promoters of oncogenic genes, and this interaction drives oncogenic gene transcription; structure-guided mutagenesis disrupting the DPF2-H3K14la interaction blunts cancer-related gene expression and cell survival.\",\n      \"method\": \"Multivalent photoaffinity probe with quantitative proteomics, biochemical binding assays, CUT&Tag chromatin mapping, structure-guided mutagenesis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (photoaffinity proteomics, biochemical assays, CUT&Tag, mutagenesis) in a single rigorous study establishing DPF2 as a bona fide H3K14la reader\",\n      \"pmids\": [\"39636855\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The tandem PHD finger domain of DPF2 directly binds acetylated tails of both histone H3 and H4 via bipartite binding pockets on the DPF2 surface; targeted mutagenesis of these pockets abolishes DPF2 recruitment to target chromatin and its ability to prevent myeloid differentiation in vivo.\",\n      \"method\": \"Crystal structure at 1.6-Å resolution, histone peptide binding assays, targeted mutagenesis, chromatin recruitment assays, in vivo myeloid differentiation assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with mutagenesis validated by functional in vivo assay, multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"28533407\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DPF2 PHD1 domain binds crotonylated H3K14 (H3K14Cr) through both PHD1 and PHD2 pockets as defined by protein footprinting mass spectrometry; this interaction is preserved when BAF45D is within the intact BAF complex, and the ATPase BRM also displays H3K14Cr-protected peptides in two domains.\",\n      \"method\": \"Protein footprinting mass spectrometry (hydroxyl radical footprinting), binding assays with isolated DPF domain and full BAF complex\",\n      \"journal\": \"ACS bio & med chem Au\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — novel footprinting MS method with orthogonal binding assays, single lab, no prior replication of this specific finding\",\n      \"pmids\": [\"39184054\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"The C2H2-type zinc finger domain of DPF2 adopts a canonical C2H2 fold with two beta strands and one alpha helix; conserved residues Lys207, Lys216, and Arg217 form a positively charged surface implicating potential DNA-binding capacity.\",\n      \"method\": \"X-ray crystal structure determination\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — crystal structure established, but DNA-binding capacity is inferred structurally and not experimentally validated in this paper\",\n      \"pmids\": [\"21888896\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"DPF2 acts as a co-repressor for ERRα by directly binding ERRα, recognizing acetylated histone H3, and associating with HDAC1; DPF2 is recruited to ERR target gene promoters in myoblast cells and its knockdown derepresses ERRα target gene mRNA levels.\",\n      \"method\": \"Biochemical purification from HeLa cells, co-immunoprecipitation, GST pulldown, ChIP, siRNA knockdown with gene expression analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal biochemical assays plus ChIP plus functional knockdown in a single lab with multiple orthogonal methods\",\n      \"pmids\": [\"20400511\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"DPF2 directly interacts with OCT4 protein, promotes its poly-ubiquitination via K48-linked ubiquitin chains, and targets it for proteasomal degradation; DPF2 PHD2 domain is required for ubiquitination activity but both wild-type and PHD2 mutant DPF2 redistribute nuclear OCT4.\",\n      \"method\": \"Co-immunoprecipitation, GST pulldown, in vitro ubiquitination assay, siRNA knockdown, overexpression in 293 cells\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro ubiquitination assay plus multiple cell-based assays (Co-IP, GST pulldown, KD/OE) in single lab\",\n      \"pmids\": [\"26417682\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Dpf2 co-occupies enhancers with Oct4, Sox2, p300, and Brg1 in ESCs; deletion of Dpf2 represses Tbx3 through loss of H3K27ac at its distal enhancer and impairs mesendodermal differentiation, which can be rescued by restoring Tbx3 expression. PRC2 subunit Eed antagonizes Dpf2-dependent Tbx3 expression by binding an intragenic Tbx3 enhancer.\",\n      \"method\": \"ChIP-seq, ATAC-seq, genetic deletion (Dpf2 KO ESCs), rescue experiments (Tbx3 re-expression), genetic epistasis (Dpf2 vs. Eed/Ezh2)\",\n      \"journal\": \"Cell stem cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with rescue, epistasis analysis, and multiple chromatin profiling methods establishing pathway position and mechanism\",\n      \"pmids\": [\"30609396\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Missense variants in DPF2 PHD1 and PHD2 domains found in Coffin-Siris syndrome abolish or impair DPF2 binding to unmodified and modified H3 histone tails; overexpression of these variants causes formation of nuclear aggregates that recruit wild-type DPF2 and BRG1, consistent with a dominant-negative mechanism.\",\n      \"method\": \"Pull-down assays with recombinant proteins and histone peptides, overexpression in HEK293 and COS7 cells, immunofluorescence\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding assays with disease mutations plus cell-based dominant-negative evidence, single lab\",\n      \"pmids\": [\"29429572\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"DPF2 functions in the non-canonical NF-κB pathway to suppress type I interferon (IFN-β) induction; knockdown of DPF2 in influenza-infected cells increases IFN-β expression, phosphorylation of STAT1, and production of antiviral proteins, while reducing viral protein expression and progeny virus by ~2 logs.\",\n      \"method\": \"RNAi screen (2,732 genes), siRNA knockdown, viral growth kinetics assay, IFN-β/cytokine measurement, Western blot for STAT1 phosphorylation\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional KD with defined signaling readouts (IFN-β, STAT1), multiple assays, single lab\",\n      \"pmids\": [\"28404846\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss of Dpf2 in macrophages reduces H3K27ac and H3K4me1 marks at the Cacna1d enhancer, impairing Cacna1d mRNA expression and reducing intracellular calcium; this attenuates MAPK signaling and promotes anti-inflammatory macrophage polarization, protecting against intestinal injury.\",\n      \"method\": \"Mouse genetic knockout, single-cell RNA sequencing, spatial transcriptomics, ChIP for histone marks, MAPK signaling assays, patient-derived organoids\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — mouse genetics with mechanistic dissection through chromatin marks, downstream signaling, and validation in human clinical samples using multiple orthogonal methods\",\n      \"pmids\": [\"41223220\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"BAF45d (DPF2) alternative splicing is regulated by PTBP1 (polypyrimidine tract-binding protein 1), and reciprocally, BAF45d regulates PTBP1 splicing activity, establishing a feedback loop between RNA splicing regulation and transcription in glioblastoma.\",\n      \"method\": \"Splicing array, mechanistic and functional studies in glioblastoma patient samples and cell lines, siRNA/overexpression experiments\",\n      \"journal\": \"Neuro-oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — reciprocal regulation demonstrated with functional assays, but abstract lacks detail on specific biochemical methods for the PTBP1–DPF2 interaction\",\n      \"pmids\": [\"29373718\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"DPF2 (along with SMARCA4/BRG1 and SMARCD2/BAF60B) is selectively required for leukaemic cell expansion and self-renewal in MLL-rearranged leukaemia; gene expression profiling shows these subunits have overlapping functions in maintaining haematopoietic stem cell-associated gene expression but are not required for c-MYC target gene expression in human cells.\",\n      \"method\": \"shRNA knockdown, gene expression profiling, in vitro and in vivo leukaemia models\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined transcriptional phenotype, but DPF2-specific mechanism partially conflated with two other subunits\",\n      \"pmids\": [\"26571505\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In H9-derived spinal cord neural stem cells (NSCs), BAF45D (DPF2) preferentially binds anterior and trunk/central HOX gene loci and the NES gene, with markedly greater chromatin enrichment compared to ESCs, and also targets TBX6, a regulator of spinal cord neural mesodermal progenitors.\",\n      \"method\": \"ChIP-seq (CUT&RUN or similar chromatin binding assay) comparing ESC vs. spinal cord NSC chromatin\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — chromatin binding data without functional perturbation experiments establishing causal role, single lab\",\n      \"pmids\": [\"38168763\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DPF2 (BAF45d) is a histone-reader subunit of the BAF (SWI/SNF) chromatin-remodeling complex whose tandem PHD finger domain directly binds acetylated, crotonylated, and lactylated histone H3/H4 tails to recruit or stabilize the BAF complex at enhancers and promoters; through this chromatin-reading activity DPF2 regulates transcriptional programs controlling myeloid differentiation, ESC pluripotency/differentiation (antagonizing PRC2 at Tbx3), macrophage inflammatory polarization via CACNA1D-MAPK signaling, and oncogene expression, while also acting as an E3-like ubiquitin ligase that targets OCT4 for K48-linked proteasomal degradation and functioning in the non-canonical NF-κB pathway to suppress innate interferon responses.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DPF2 (BAF45d) is a histone-reader subunit of the BAF (SWI/SNF) chromatin-remodeling complex that couples recognition of modified histone tails to the regulation of cell-type-specific transcriptional programs [#1, #6]. Its tandem PHD finger module directly binds acetylated histone H3 and H4 tails through bipartite binding pockets, and structure-guided mutation of these pockets abolishes DPF2 chromatin recruitment and its ability to block myeloid differentiation [#1]. This reader activity extends beyond acetylation to other acyl marks: DPF2 engages crotonylated H3K14 through its PHD1/PHD2 pockets while embedded in the intact BAF complex [#2], and binds H3K14 lactylation to drive transcription of oncogenic genes, where disrupting the DPF2–H3K14la interaction blunts cancer-gene expression and cell survival [#0]. In embryonic stem cells DPF2 co-occupies enhancers with OCT4, SOX2, p300, and BRG1, and is required for Tbx3 expression via H3K27ac at its distal enhancer, antagonizing the PRC2 subunit EED to enable mesendodermal differentiation [#6]; an analogous enhancer-licensing role operates in macrophages, where DPF2 sustains H3K27ac/H3K4me1 at the Cacna1d enhancer to promote calcium-dependent MAPK signaling and inflammatory polarization [#9]. DPF2 also acts as a transcriptional co-repressor for ERR\\u03b1 in association with HDAC1 [#4], promotes K48-linked polyubiquitination and proteasomal degradation of OCT4 in a manner requiring its PHD2 domain [#5], and functions in the non-canonical NF-\\u03baB pathway to suppress type I interferon induction during influenza infection [#8]. Heterozygous missense variants in the PHD1/PHD2 domains cause Coffin-Siris syndrome, impairing histone-tail binding and acting through a dominant-negative mechanism that sequesters wild-type DPF2 and BRG1 [#7].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Established that DPF2 is not merely a structural subunit but a transcriptional regulator, acting as a co-repressor that links a nuclear receptor to histone deacetylase activity.\",\n      \"evidence\": \"Biochemical purification, Co-IP/GST pulldown, ChIP, and siRNA knockdown in myoblasts\",\n      \"pmids\": [\"20400511\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not resolve whether repression depends on PHD-domain histone reading versus HDAC1 recruitment\", \"Generality beyond ERR\\u03b1 targets untested\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined the structure of the DPF2 C2H2 zinc finger, raising the possibility of a DNA-contacting surface in addition to histone reading.\",\n      \"evidence\": \"X-ray crystal structure of the C2H2 domain\",\n      \"pmids\": [\"21888896\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"DNA-binding capacity inferred from surface charge only, not experimentally validated\", \"Functional relevance of the proposed DNA contacts unknown\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Revealed a non-chromatin enzymatic role: DPF2 directs K48-linked ubiquitination and proteasomal degradation of the pluripotency factor OCT4, connecting it to control of the pluripotency network.\",\n      \"evidence\": \"Co-IP, GST pulldown, in vitro ubiquitination, knockdown/overexpression in 293 cells\",\n      \"pmids\": [\"26417682\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether DPF2 is the direct E3 ligase or a recruiting adaptor not resolved\", \"PHD2 requirement for ubiquitination mechanistically unexplained\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Placed DPF2 within a functionally required BAF subunit set for MLL-rearranged leukaemia, framing it as a dependency in oncogenic transcriptional maintenance.\",\n      \"evidence\": \"shRNA knockdown with gene expression profiling and in vitro/in vivo leukaemia models\",\n      \"pmids\": [\"26571505\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"DPF2-specific contribution partially conflated with SMARCA4 and SMARCD2\", \"Direct target genes of DPF2 in this context not isolated\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Provided the structural basis for DPF2 as a dual-acetyl reader, showing the tandem PHD module binds acetylated H3 and H4 tails and that this reading is functionally required to block myeloid differentiation.\",\n      \"evidence\": \"1.6-\\u00c5 crystal structure, histone peptide binding, targeted mutagenesis, in vivo myeloid differentiation assay\",\n      \"pmids\": [\"28533407\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not address acyl marks beyond acetylation\", \"Did not map genome-wide targets controlled by this reading activity\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identified a signaling role beyond chromatin, showing DPF2 in the non-canonical NF-\\u03baB pathway restrains type I interferon antiviral responses.\",\n      \"evidence\": \"RNAi screen, siRNA knockdown, viral growth kinetics, IFN-\\u03b2/STAT1 readouts in influenza-infected cells\",\n      \"pmids\": [\"28404846\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular link between DPF2 and NF-\\u03baB components undefined\", \"Unclear whether this requires BAF complex or histone-reading activity\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Established DPF2 as a Coffin-Siris syndrome gene and connected disease variants mechanistically to loss of histone-tail binding and dominant-negative sequestration of BAF.\",\n      \"evidence\": \"Recombinant pull-down with histone peptides, overexpression and immunofluorescence in HEK293/COS7\",\n      \"pmids\": [\"29429572\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Dominant-negative aggregate behavior shown by overexpression, not endogenous variants\", \"Tissue-specific developmental consequences not modeled\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Linked DPF2 to an RNA-splicing feedback loop with PTBP1, expanding its regulatory reach from transcription into splicing in glioblastoma.\",\n      \"evidence\": \"Splicing array and functional siRNA/overexpression studies in glioblastoma samples and cell lines\",\n      \"pmids\": [\"29373718\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Biochemical basis of the DPF2\\u2013PTBP1 interaction not detailed\", \"Direct versus indirect reciprocal regulation unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Positioned DPF2 in the ESC enhancer network, showing it co-occupies pluripotency enhancers and licenses Tbx3 expression by antagonizing PRC2 to enable mesendodermal differentiation.\",\n      \"evidence\": \"ChIP-seq, ATAC-seq, Dpf2 KO ESCs with Tbx3 rescue and Dpf2/Eed epistasis\",\n      \"pmids\": [\"30609396\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How DPF2 reading translates into H3K27ac deposition at the enhancer not fully resolved\", \"Mechanism of antagonism with EED at the intragenic enhancer not detailed\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Extended DPF2 reading specificity to crotonylation, demonstrating PHD-mediated engagement of H3K14Cr is preserved within the assembled BAF complex.\",\n      \"evidence\": \"Hydroxyl radical protein footprinting MS with binding assays on isolated DPF domain and full BAF complex\",\n      \"pmids\": [\"39184054\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional/transcriptional consequence of H3K14Cr reading not tested\", \"Single-lab footprinting method not independently replicated\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined DPF2 as a histone lactylation reader and tied this directly to oncogenic transcription, showing disruption of the H3K14la interaction impairs cancer-gene expression and cell survival.\",\n      \"evidence\": \"Photoaffinity proteomics, biochemical binding, CUT&Tag, structure-guided mutagenesis\",\n      \"pmids\": [\"39636855\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of the full oncogenic gene set governed by H3K14la reading incomplete\", \"In vivo tumor dependence not established\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Mapped a developmental-stage shift in DPF2 chromatin targeting, showing preferential binding of anterior/trunk HOX loci, NES, and TBX6 in spinal cord neural stem cells.\",\n      \"evidence\": \"Chromatin binding profiling (CUT&RUN-type) comparing ESCs and spinal cord NSCs\",\n      \"pmids\": [\"38168763\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Descriptive binding data without functional perturbation establishing causal role\", \"Single lab, no rescue or knockout validation\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated an in vivo enhancer-licensing role in immune cells, where DPF2 sustains Cacna1d enhancer marks to drive calcium-dependent MAPK signaling and inflammatory macrophage polarization.\",\n      \"evidence\": \"Mouse KO, scRNA-seq, spatial transcriptomics, ChIP for histone marks, MAPK assays, patient organoids\",\n      \"pmids\": [\"41223220\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct DPF2 reading of a specific acyl mark at the Cacna1d enhancer not pinpointed\", \"Whether MAPK attenuation is solely Cacna1d-dependent untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How DPF2's distinct activities \\u2014 multivalent histone acyl reading, BAF recruitment, ERR\\u03b1 co-repression, OCT4 ubiquitination, and NF-\\u03baB signaling \\u2014 are integrated and switched between contexts remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No unifying model linking chromatin-reading to the ubiquitin-ligase activity\", \"Determinants of cell-type-specific target selection (HOX vs. enhancers vs. oncogenes) unknown\", \"Whether NF-\\u03baB and splicing roles depend on BAF complex membership untested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0, 1, 2, 7]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [4, 6]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [5, 7]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0, 1, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 1, 6]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [4, 6, 9]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [6, 12]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [8, 9]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"complexes\": [\"BAF (SWI/SNF) complex\"],\n    \"partners\": [\"SMARCA4\", \"OCT4\", \"ESRRA\", \"HDAC1\", \"SOX2\", \"EP300\", \"EED\", \"PTBP1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}