{"gene":"YAF2","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2020,"finding":"YAF2 specifically binds H2AK119ub1 and recruits the YAF2-PRC1 complex to catalyse ubiquitination of H2A on neighbouring nucleosomes through a positive-feedback model, propagating H2AK119ub1 during cell division; histone H1-compacted chromatin enhances distal propagation of this mark.","method":"Biochemical binding assays, chromatin fractionation, cell division assays; disruption of RYBP/YAF2-PRC1 activity or H1-dependent compaction caused significant loss of H2AK119ub1 maintenance","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (binding assays, functional disruption, cell division readout), published in high-impact journal, mechanistically detailed","pmids":["32203418"],"is_preprint":false},{"year":2013,"finding":"YAF2 bridges the interaction between YY1 and the PRC1 complex; YAF2 is responsible for PcG recruitment to DNA, which is mediated by YY1 DNA binding. Knock-down of YY1 abrogated PcG recruitment even when exogenous YAF2 was present, showing YY1 DNA binding is a prerequisite for Polycomb assembly. YAF2 and RYBP regulate largely distinct sets of Polycomb target genes.","method":"Co-IP, ChIP assays in HeLa cells, YY1 knock-down, rescue with exogenous YAF2, dRYBP mutant fly complementation with mouse YAF2","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, ChIP, genetic rescue across species, multiple orthogonal methods in one study","pmids":["24285299"],"is_preprint":false},{"year":2002,"finding":"YAF2 interacts with hGABPβ and YY1 both in vitro and in vivo, and positively regulates transcriptional activity of hGABP, functionally distinct from YEAF1/RYBP which negatively regulates hGABP activity.","method":"Yeast two-hybrid screening, yeast three-hybrid assay, in vitro and in vivo binding assays, transcriptional reporter assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid plus in vitro and in vivo binding confirmed, functional transcriptional assays, single lab","pmids":["11953439"],"is_preprint":false},{"year":2010,"finding":"The YY1 REPO domain (25 amino acids) interacts with YAF2 and recruits YAF2 to DNA; deletion of the REPO domain abolishes this interaction. YAF2, when fused to a heterologous DNA-binding domain, can recruit PcG proteins to DNA and mediate transcriptional repression. Mutation of the Drosophila YAF2 homolog (dRYBP) reduces PcG recruitment to DNA.","method":"Co-IP, transcriptional repression assays with heterologous DNA-binding domain fusion, deletion mutagenesis of YY1 REPO domain, Drosophila dRYBP mutant analysis","journal":"Journal of cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — deletion mutagenesis, functional transcriptional assays, in vivo Drosophila genetics, single lab","pmids":["19960508"],"is_preprint":false},{"year":2006,"finding":"Zebrafish Yaf2 is required for cell survival during embryogenesis; depletion activates widespread caspase 8-mediated apoptosis and causes developmental arrest. Human YAF2 mRNA rescues this phenotype, and YAF2 inhibits caspase 8-mediated apoptosis in cultured cells.","method":"Morpholino knockdown in zebrafish, caspase inhibitor rescue (pan-caspase and caspase 8-specific), human YAF2 mRNA rescue, apoptosis assays in cultured cells","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — morpholino knockdown with multiple rescue strategies (mRNA, caspase inhibitors), functional cellular assays, single lab","pmids":["16891308"],"is_preprint":false},{"year":2001,"finding":"YAF2 binds to the central region of MycN in vitro and in vivo, localizes to the nucleus, and enhances MycN-mediated transactivation from an E-box promoter; deletion of the YAF2-binding region in MycN abrogates this enhancement.","method":"Yeast two-hybrid, in vitro binding assay, in vivo co-immunoprecipitation, nuclear localization by cell imaging, E-box reporter transactivation assay, deletion mutagenesis of MycN","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid confirmed by in vitro and in vivo binding, functional transactivation assay with deletion mutagenesis, single lab","pmids":["11593398"],"is_preprint":false},{"year":2003,"finding":"YAF2 binds to the Myc protein in vivo and in vitro, but in contrast to its activating effect on MycN, YAF2 inhibits Myc-mediated transactivation and transformation.","method":"In vitro binding, in vivo co-immunoprecipitation, transcriptional reporter assays, transformation assays","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro and in vivo binding with functional assays, single lab, corroborates earlier MycN study","pmids":["12706874"],"is_preprint":false},{"year":2003,"finding":"Mouse YAF2 interacts with Ring1B (and Ring1A), a constituent of mammalian PcG complexes; biochemical and colocalization evidence in tissue culture cells supports YAF2 involvement in PcG complexes together with Ring1B/Ring1A.","method":"Co-immunoprecipitation, colocalization studies in tissue culture cells, identification of two YAF2 isoforms by alternative splicing","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP and colocalization, single lab, corroborated by multiple subsequent studies on YAF2-PRC1 interaction","pmids":["14557078"],"is_preprint":false},{"year":2015,"finding":"YAF2 binds PDCD5 and stabilizes it by inhibiting ubiquitin-dependent proteasomal degradation, thereby promoting TP53 activation during genotoxic stress. YAF2 knockdown reduces PDCD5 protein (not mRNA) levels. YAF2 promotion of TP53 activation is abolished by PDCD5 deletion and restored by wild-type PDCD5 but not by YAF2-interaction-defective PDCD5 mutants.","method":"Yeast two-hybrid screen, co-IP, siRNA knockdown, ubiquitination assays, genotoxic stress assays (etoposide), apoptosis rescue with PDCD5 mutants","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid confirmed by Co-IP, mechanistic rescue with interaction-defective mutants, single lab","pmids":["25603536"],"is_preprint":false},{"year":2018,"finding":"YAF2 assembles into a noncanonical PRC1 complex via a region encompassing amino acid residues 102–150. Serine 166 is a YAF2 phosphorylation site; S166A mutation compromises Ring1B-mediated H2A monoubiquitination and repression of target genes. Yaf2 deletion in mESCs causes compromised proliferation, abnormal differentiation, and de-repression of ectoderm-associated genes.","method":"Yeast two-hybrid, co-IP, deletion mutagenesis (residues 102–150), phosphorylation site mutagenesis (S166A), genome-wide profiling (ChIP-seq), H2A ubiquitination assays, mESC knockout","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods including in vitro ubiquitination assay, site-directed mutagenesis, genome-wide profiling, and KO phenotype in single rigorous study","pmids":["29959227"],"is_preprint":false},{"year":2021,"finding":"YAF2 mediates interaction between YY1 and SIRT6; pulldown assays show YAF2 associates with both YY1 and SIRT6 at a 1:1:1 molar ratio. YAF2 and YY1 accelerate SIRT6-induced H3K9 deacetylation at the TFAM gene upstream region, contributing to age-related mitochondrial downregulation.","method":"Pulldown assays, protein cross-linking (molar ratio determination), ChIP-qPCR for H3K9 deacetylation, mRNA transfection experiments, SIRT6 inhibitor treatment","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pulldown with molar ratio determination, ChIP-qPCR functional validation, single lab in tunicate model","pmids":["33875574"],"is_preprint":false},{"year":2021,"finding":"Phosphorylated YAF2 (at Serine 167) inhibits proteasomal degradation of polyubiquitinated FANK1 by binding to the FN3 domain of FANK1 via the amino-terminal region of YAF2, increasing FANK1 stability and thereby inhibiting tumor cell apoptosis in a FANK1-dependent manner.","method":"Co-IP, siRNA knockdown, proteasome inhibitor assays, domain mapping (FN3 domain of FANK1 binds N-terminus of YAF2), phosphorylation analysis, apoptosis assays","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with domain mapping, functional apoptosis assays, single lab, two orthogonal methods","pmids":["33784512"],"is_preprint":false},{"year":2023,"finding":"RYBP and YAF2 have distinct regulatory functions in neural differentiation: Rybp knockout impairs neural differentiation by activating Wnt signaling; Yaf2 knockout promotes neural differentiation and leads to redistribution of RYBP binding with increased RYBP and H2AK119ub enrichment on RYBP-YAF2 co-targeted genes, preventing ectopic derepression of non-neuroectoderm genes.","method":"Knockout mESC lines (Rybp KO, Yaf2 KO), ChIP-seq for RYBP and H2AK119ub, genome-wide transcriptional profiling, neural differentiation assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with genome-wide ChIP-seq and transcriptional profiling, multiple orthogonal methods, peer-reviewed high-impact journal","pmids":["37935677"],"is_preprint":false}],"current_model":"YAF2 is a component of variant Polycomb Repressive Complex 1 (vPRC1) that reads H2AK119ub1 to recruit vPRC1 and propagate this mark via a positive-feedback mechanism, bridges YY1 to PRC1 for sequence-specific Polycomb recruitment, stabilizes PDCD5 to promote TP53-mediated apoptotic signaling during genotoxic stress, inhibits caspase 8-mediated apoptosis in a survival context, modulates MycN and Myc transcriptional activity differentially, and is regulated by phosphorylation at Ser166/167 which controls both Ring1B-mediated H2A ubiquitination and anti-apoptotic activity through FANK1 stabilization."},"narrative":{"mechanistic_narrative":"YAF2 is a substoichiometric component of variant (noncanonical) Polycomb Repressive Complex 1 that couples Polycomb recruitment to maintenance of the repressive H2AK119ub1 mark and thereby controls developmental gene silencing [PMID:32203418, PMID:29959227]. It assembles into vPRC1 through a region spanning residues 102–150 and partners with the catalytic E3 ligase Ring1B (and Ring1A) to drive H2A monoubiquitination [PMID:29959227, PMID:14557078]. As a reader-writer module, YAF2 binds H2AK119ub1 and directs the YAF2-PRC1 complex to ubiquitinate H2A on neighboring nucleosomes, a positive-feedback mechanism that propagates the mark through cell division and is enhanced by histone H1-compacted chromatin [PMID:32203418]. Sequence-specific targeting is achieved by bridging the transcription factor YY1 to PRC1: YAF2 binds the YY1 REPO domain and YY1 DNA binding is a prerequisite for Polycomb assembly at target loci [PMID:24285299, PMID:19960508]. YAF2 phosphorylation at Ser166 is required for efficient Ring1B-mediated H2A ubiquitination and target-gene repression, and loss of Yaf2 in embryonic stem cells compromises proliferation, perturbs differentiation, and de-represses lineage genes [PMID:29959227, PMID:37935677]. YAF2 and its paralog RYBP regulate largely distinct Polycomb target sets and have opposing effects on neural differentiation [PMID:24285299, PMID:37935677]. Beyond chromatin, YAF2 binds and differentially modulates MycN (activating) versus Myc (inhibitory) transcriptional activity [PMID:11593398, PMID:12706874], stabilizes PDCD5 to promote TP53-dependent apoptotic signaling under genotoxic stress [PMID:25603536], and, when phosphorylated, stabilizes FANK1 to suppress apoptosis [PMID:33784512].","teleology":[{"year":2001,"claim":"Established YAF2 as a Myc-family transcriptional cofactor by showing it binds the central region of nuclear MycN and enhances E-box-driven transactivation, framing an early non-chromatin function.","evidence":"Yeast two-hybrid, in vitro/in vivo binding, E-box reporter and MycN deletion mutagenesis","pmids":["11593398"],"confidence":"Medium","gaps":["Mechanism by which YAF2 boosts MycN activity unresolved","No genome-wide MycN target validation"]},{"year":2002,"claim":"Showed YAF2 interacts with hGABPβ and YY1 and positively regulates transcription, contrasting it functionally with RYBP and hinting at distinct paralog roles.","evidence":"Yeast two/three-hybrid, in vitro/in vivo binding, transcriptional reporter assays","pmids":["11953439"],"confidence":"Medium","gaps":["Direct chromatin occupancy not demonstrated","Relationship of GABP activation to Polycomb function unclear"]},{"year":2003,"claim":"Connected YAF2 to the Polycomb machinery by demonstrating its interaction with Ring1B/Ring1A, placing it within mammalian PcG complexes.","evidence":"Co-IP and colocalization in tissue culture, identification of splice isoforms","pmids":["14557078"],"confidence":"Medium","gaps":["Catalytic consequence of YAF2-Ring1B interaction not yet shown","Target genes undefined"]},{"year":2003,"claim":"Revealed opposing regulation within the Myc family by showing YAF2 inhibits Myc-mediated transactivation and transformation, unlike its activating effect on MycN.","evidence":"In vitro/in vivo binding, reporter and transformation assays","pmids":["12706874"],"confidence":"Medium","gaps":["Structural basis for opposite Myc vs MycN effects unknown","In vivo relevance to tumorigenesis untested"]},{"year":2006,"claim":"Demonstrated an essential survival function for YAF2 in vivo, as depletion in zebrafish triggers caspase 8-mediated apoptosis rescuable by human YAF2, establishing an anti-apoptotic role.","evidence":"Morpholino knockdown, caspase-inhibitor and mRNA rescue, apoptosis assays","pmids":["16891308"],"confidence":"Medium","gaps":["Molecular link between YAF2 and caspase 8 not defined","Relationship to Polycomb activity unaddressed"]},{"year":2010,"claim":"Mapped sequence-specific Polycomb recruitment to the YY1 REPO domain–YAF2 interaction, showing YAF2 can recruit PcG proteins and repress transcription when tethered to DNA.","evidence":"Co-IP, REPO deletion mutagenesis, heterologous DNA-binding domain fusion repression, Drosophila dRYBP genetics","pmids":["19960508"],"confidence":"Medium","gaps":["Endogenous YY1-YAF2 target loci not enumerated","Stoichiometry of bridging complex unknown"]},{"year":2013,"claim":"Defined YAF2 as the obligate bridge between YY1 DNA binding and PRC1 recruitment and distinguished its target gene set from RYBP, clarifying paralog-specific Polycomb function.","evidence":"Reciprocal Co-IP, ChIP, YY1 knockdown/rescue, cross-species dRYBP complementation","pmids":["24285299"],"confidence":"High","gaps":["Genome-wide map of YY1-dependent vs independent YAF2 targets incomplete","How distinct YAF2 vs RYBP targeting is achieved unknown"]},{"year":2015,"claim":"Identified a TP53-axis function: YAF2 binds and stabilizes PDCD5 against proteasomal degradation to promote TP53 activation during genotoxic stress.","evidence":"Yeast two-hybrid, Co-IP, siRNA, ubiquitination assays, etoposide stress, PDCD5 mutant rescue","pmids":["25603536"],"confidence":"Medium","gaps":["How YAF2 protects PDCD5 from ubiquitination mechanistically unclear","Reconciliation with anti-apoptotic role not addressed"]},{"year":2018,"claim":"Provided the integrated chromatin mechanism: YAF2 assembles into noncanonical PRC1 via residues 102–150 and its Ser166 phosphorylation is required for Ring1B-driven H2A ubiquitination, with Yaf2 loss in mESCs causing differentiation defects and gene de-repression.","evidence":"Co-IP, deletion and S166A mutagenesis, ChIP-seq, in vitro H2A ubiquitination, mESC knockout","pmids":["29959227"],"confidence":"High","gaps":["Kinase responsible for Ser166 phosphorylation unidentified","Structural detail of the 102–150 assembly region absent"]},{"year":2020,"claim":"Established YAF2 as a reader-writer that propagates H2AK119ub1 through a positive-feedback loop, explaining heritable maintenance of the mark across cell division.","evidence":"Biochemical binding assays, chromatin fractionation, H1-compaction and cell division readouts, RYBP/YAF2-PRC1 disruption","pmids":["32203418"],"confidence":"High","gaps":["Quantitative contribution of YAF2 vs RYBP to propagation in vivo unclear","How H1 compaction enhances distal spreading mechanistically undefined"]},{"year":2021,"claim":"Extended YAF2's adaptor role to chromatin-modifying deacetylation by showing it bridges YY1 and SIRT6 at 1:1:1 stoichiometry to accelerate H3K9 deacetylation and mitochondrial gene downregulation.","evidence":"Pulldown, cross-linking molar ratio, ChIP-qPCR, SIRT6 inhibition (tunicate model)","pmids":["33875574"],"confidence":"Medium","gaps":["Relevance to mammalian aging untested","Independence from PRC1 function unclear"]},{"year":2021,"claim":"Provided a phosphorylation-dependent anti-apoptotic mechanism: phospho-Ser167 YAF2 stabilizes polyubiquitinated FANK1 by binding its FN3 domain, suppressing tumor cell apoptosis.","evidence":"Co-IP, siRNA, proteasome inhibition, FN3/N-terminus domain mapping, phosphorylation and apoptosis assays","pmids":["33784512"],"confidence":"Medium","gaps":["Kinase and signaling input for Ser167 unknown","Relationship between Ser166 (chromatin) and Ser167 (FANK1) phosphorylation events unresolved"]},{"year":2023,"claim":"Resolved divergent paralog function in differentiation: Yaf2 loss redistributes RYBP and H2AK119ub onto co-targeted genes and promotes neural differentiation, opposite to Rybp loss, showing YAF2 restrains ectopic lineage gene activation.","evidence":"Rybp and Yaf2 KO mESCs, RYBP and H2AK119ub ChIP-seq, transcriptional profiling, neural differentiation assays","pmids":["37935677"],"confidence":"High","gaps":["Mechanism driving RYBP redistribution upon Yaf2 loss undefined","Direct interplay with Wnt signaling not dissected for YAF2"]},{"year":null,"claim":"How YAF2's chromatin (vPRC1/H2AK119ub1) functions are mechanistically coordinated with its apoptosis-regulating roles (PDCD5/TP53 activation versus caspase 8 and FANK1-dependent survival), and which kinases control its functionally critical Ser166/Ser167 phosphorylation, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Upstream kinase for Ser166/167 unidentified","No unified model reconciling pro- and anti-apoptotic activities","No structural model of YAF2 in vPRC1 or its phospho-regulated states"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1,3,9,10]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[2,5,6]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[0]},{"term_id":"GO:0140313","term_label":"molecular sequestering activity","supporting_discovery_ids":[8,11]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[5,7]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[0,9]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,9,12]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,3,5,6]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[4,9,12]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[4,8,11]}],"complexes":["variant Polycomb Repressive Complex 1 (vPRC1)"],"partners":["RING1B","YY1","MYCN","MYC","PDCD5","FANK1","SIRT6","GABPB1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8IY57","full_name":"YY1-associated factor 2","aliases":[],"length_aa":180,"mass_kda":19.9,"function":"Binds to MYC and inhibits MYC-mediated transactivation. Also binds to MYCN and enhances MYCN-dependent transcriptional activation. Increases calpain 2-mediated proteolysis of YY1 in vitro. Component of the E2F6.com-1 complex, a repressive complex that methylates 'Lys-9' of histone H3, suggesting that it is involved in chromatin-remodeling","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q8IY57/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/YAF2","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CSNK2B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/YAF2","total_profiled":1310},"omim":[{"mim_id":"617407","title":"POLYCOMB GROUP RING FINGER PROTEIN 5; PCGF5","url":"https://www.omim.org/entry/617407"},{"mim_id":"607535","title":"RING1- AND YY1-BINDING PROTEIN; RYBP","url":"https://www.omim.org/entry/607535"},{"mim_id":"607534","title":"YY1-ASSOCIATED FACTOR 2; YAF2","url":"https://www.omim.org/entry/607534"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/YAF2"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q8IY57","domains":[{"cath_id":"4.10.1060","chopping":"19-50_108-131","consensus_level":"medium","plddt":89.9543,"start":19,"end":131}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IY57","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IY57-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IY57-F1-predicted_aligned_error_v6.png","plddt_mean":68.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=YAF2","jax_strain_url":"https://www.jax.org/strain/search?query=YAF2"},"sequence":{"accession":"Q8IY57","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8IY57.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8IY57/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IY57"}},"corpus_meta":[{"pmid":"32203418","id":"PMC_32203418","title":"RYBP/YAF2-PRC1 complexes and histone H1-dependent chromatin compaction mediate propagation of H2AK119ub1 during cell division.","date":"2020","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/32203418","citation_count":93,"is_preprint":false},{"pmid":"24285299","id":"PMC_24285299","title":"YY1 DNA binding and interaction with YAF2 is essential for Polycomb recruitment.","date":"2013","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/24285299","citation_count":54,"is_preprint":false},{"pmid":"35936223","id":"PMC_35936223","title":"Human Amniotic Fluid Mesenchymal Stem Cell-Derived Exosomes Inhibit Apoptosis in Ovarian Granulosa Cell via miR-369-3p/YAF2/PDCD5/p53 Pathway.","date":"2022","source":"Oxidative medicine and cellular longevity","url":"https://pubmed.ncbi.nlm.nih.gov/35936223","citation_count":54,"is_preprint":false},{"pmid":"11953439","id":"PMC_11953439","title":"YEAF1/RYBP and YAF-2 are functionally distinct members of a cofactor family for the YY1 and E4TF1/hGABP 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disease","url":"https://pubmed.ncbi.nlm.nih.gov/40432551","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12496,"output_tokens":3494,"usd":0.044949,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10975,"output_tokens":4440,"usd":0.082937,"stage2_stop_reason":"end_turn"},"total_usd":0.127886,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"YAF2 specifically binds H2AK119ub1 and recruits the YAF2-PRC1 complex to catalyse ubiquitination of H2A on neighbouring nucleosomes through a positive-feedback model, propagating H2AK119ub1 during cell division; histone H1-compacted chromatin enhances distal propagation of this mark.\",\n      \"method\": \"Biochemical binding assays, chromatin fractionation, cell division assays; disruption of RYBP/YAF2-PRC1 activity or H1-dependent compaction caused significant loss of H2AK119ub1 maintenance\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (binding assays, functional disruption, cell division readout), published in high-impact journal, mechanistically detailed\",\n      \"pmids\": [\"32203418\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"YAF2 bridges the interaction between YY1 and the PRC1 complex; YAF2 is responsible for PcG recruitment to DNA, which is mediated by YY1 DNA binding. Knock-down of YY1 abrogated PcG recruitment even when exogenous YAF2 was present, showing YY1 DNA binding is a prerequisite for Polycomb assembly. YAF2 and RYBP regulate largely distinct sets of Polycomb target genes.\",\n      \"method\": \"Co-IP, ChIP assays in HeLa cells, YY1 knock-down, rescue with exogenous YAF2, dRYBP mutant fly complementation with mouse YAF2\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, ChIP, genetic rescue across species, multiple orthogonal methods in one study\",\n      \"pmids\": [\"24285299\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"YAF2 interacts with hGABPβ and YY1 both in vitro and in vivo, and positively regulates transcriptional activity of hGABP, functionally distinct from YEAF1/RYBP which negatively regulates hGABP activity.\",\n      \"method\": \"Yeast two-hybrid screening, yeast three-hybrid assay, in vitro and in vivo binding assays, transcriptional reporter assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid plus in vitro and in vivo binding confirmed, functional transcriptional assays, single lab\",\n      \"pmids\": [\"11953439\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The YY1 REPO domain (25 amino acids) interacts with YAF2 and recruits YAF2 to DNA; deletion of the REPO domain abolishes this interaction. YAF2, when fused to a heterologous DNA-binding domain, can recruit PcG proteins to DNA and mediate transcriptional repression. Mutation of the Drosophila YAF2 homolog (dRYBP) reduces PcG recruitment to DNA.\",\n      \"method\": \"Co-IP, transcriptional repression assays with heterologous DNA-binding domain fusion, deletion mutagenesis of YY1 REPO domain, Drosophila dRYBP mutant analysis\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — deletion mutagenesis, functional transcriptional assays, in vivo Drosophila genetics, single lab\",\n      \"pmids\": [\"19960508\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Zebrafish Yaf2 is required for cell survival during embryogenesis; depletion activates widespread caspase 8-mediated apoptosis and causes developmental arrest. Human YAF2 mRNA rescues this phenotype, and YAF2 inhibits caspase 8-mediated apoptosis in cultured cells.\",\n      \"method\": \"Morpholino knockdown in zebrafish, caspase inhibitor rescue (pan-caspase and caspase 8-specific), human YAF2 mRNA rescue, apoptosis assays in cultured cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — morpholino knockdown with multiple rescue strategies (mRNA, caspase inhibitors), functional cellular assays, single lab\",\n      \"pmids\": [\"16891308\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"YAF2 binds to the central region of MycN in vitro and in vivo, localizes to the nucleus, and enhances MycN-mediated transactivation from an E-box promoter; deletion of the YAF2-binding region in MycN abrogates this enhancement.\",\n      \"method\": \"Yeast two-hybrid, in vitro binding assay, in vivo co-immunoprecipitation, nuclear localization by cell imaging, E-box reporter transactivation assay, deletion mutagenesis of MycN\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid confirmed by in vitro and in vivo binding, functional transactivation assay with deletion mutagenesis, single lab\",\n      \"pmids\": [\"11593398\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"YAF2 binds to the Myc protein in vivo and in vitro, but in contrast to its activating effect on MycN, YAF2 inhibits Myc-mediated transactivation and transformation.\",\n      \"method\": \"In vitro binding, in vivo co-immunoprecipitation, transcriptional reporter assays, transformation assays\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro and in vivo binding with functional assays, single lab, corroborates earlier MycN study\",\n      \"pmids\": [\"12706874\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Mouse YAF2 interacts with Ring1B (and Ring1A), a constituent of mammalian PcG complexes; biochemical and colocalization evidence in tissue culture cells supports YAF2 involvement in PcG complexes together with Ring1B/Ring1A.\",\n      \"method\": \"Co-immunoprecipitation, colocalization studies in tissue culture cells, identification of two YAF2 isoforms by alternative splicing\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP and colocalization, single lab, corroborated by multiple subsequent studies on YAF2-PRC1 interaction\",\n      \"pmids\": [\"14557078\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"YAF2 binds PDCD5 and stabilizes it by inhibiting ubiquitin-dependent proteasomal degradation, thereby promoting TP53 activation during genotoxic stress. YAF2 knockdown reduces PDCD5 protein (not mRNA) levels. YAF2 promotion of TP53 activation is abolished by PDCD5 deletion and restored by wild-type PDCD5 but not by YAF2-interaction-defective PDCD5 mutants.\",\n      \"method\": \"Yeast two-hybrid screen, co-IP, siRNA knockdown, ubiquitination assays, genotoxic stress assays (etoposide), apoptosis rescue with PDCD5 mutants\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid confirmed by Co-IP, mechanistic rescue with interaction-defective mutants, single lab\",\n      \"pmids\": [\"25603536\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"YAF2 assembles into a noncanonical PRC1 complex via a region encompassing amino acid residues 102–150. Serine 166 is a YAF2 phosphorylation site; S166A mutation compromises Ring1B-mediated H2A monoubiquitination and repression of target genes. Yaf2 deletion in mESCs causes compromised proliferation, abnormal differentiation, and de-repression of ectoderm-associated genes.\",\n      \"method\": \"Yeast two-hybrid, co-IP, deletion mutagenesis (residues 102–150), phosphorylation site mutagenesis (S166A), genome-wide profiling (ChIP-seq), H2A ubiquitination assays, mESC knockout\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods including in vitro ubiquitination assay, site-directed mutagenesis, genome-wide profiling, and KO phenotype in single rigorous study\",\n      \"pmids\": [\"29959227\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"YAF2 mediates interaction between YY1 and SIRT6; pulldown assays show YAF2 associates with both YY1 and SIRT6 at a 1:1:1 molar ratio. YAF2 and YY1 accelerate SIRT6-induced H3K9 deacetylation at the TFAM gene upstream region, contributing to age-related mitochondrial downregulation.\",\n      \"method\": \"Pulldown assays, protein cross-linking (molar ratio determination), ChIP-qPCR for H3K9 deacetylation, mRNA transfection experiments, SIRT6 inhibitor treatment\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pulldown with molar ratio determination, ChIP-qPCR functional validation, single lab in tunicate model\",\n      \"pmids\": [\"33875574\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Phosphorylated YAF2 (at Serine 167) inhibits proteasomal degradation of polyubiquitinated FANK1 by binding to the FN3 domain of FANK1 via the amino-terminal region of YAF2, increasing FANK1 stability and thereby inhibiting tumor cell apoptosis in a FANK1-dependent manner.\",\n      \"method\": \"Co-IP, siRNA knockdown, proteasome inhibitor assays, domain mapping (FN3 domain of FANK1 binds N-terminus of YAF2), phosphorylation analysis, apoptosis assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with domain mapping, functional apoptosis assays, single lab, two orthogonal methods\",\n      \"pmids\": [\"33784512\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RYBP and YAF2 have distinct regulatory functions in neural differentiation: Rybp knockout impairs neural differentiation by activating Wnt signaling; Yaf2 knockout promotes neural differentiation and leads to redistribution of RYBP binding with increased RYBP and H2AK119ub enrichment on RYBP-YAF2 co-targeted genes, preventing ectopic derepression of non-neuroectoderm genes.\",\n      \"method\": \"Knockout mESC lines (Rybp KO, Yaf2 KO), ChIP-seq for RYBP and H2AK119ub, genome-wide transcriptional profiling, neural differentiation assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with genome-wide ChIP-seq and transcriptional profiling, multiple orthogonal methods, peer-reviewed high-impact journal\",\n      \"pmids\": [\"37935677\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"YAF2 is a component of variant Polycomb Repressive Complex 1 (vPRC1) that reads H2AK119ub1 to recruit vPRC1 and propagate this mark via a positive-feedback mechanism, bridges YY1 to PRC1 for sequence-specific Polycomb recruitment, stabilizes PDCD5 to promote TP53-mediated apoptotic signaling during genotoxic stress, inhibits caspase 8-mediated apoptosis in a survival context, modulates MycN and Myc transcriptional activity differentially, and is regulated by phosphorylation at Ser166/167 which controls both Ring1B-mediated H2A ubiquitination and anti-apoptotic activity through FANK1 stabilization.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"YAF2 is a substoichiometric component of variant (noncanonical) Polycomb Repressive Complex 1 that couples Polycomb recruitment to maintenance of the repressive H2AK119ub1 mark and thereby controls developmental gene silencing [#0, #9]. It assembles into vPRC1 through a region spanning residues 102–150 and partners with the catalytic E3 ligase Ring1B (and Ring1A) to drive H2A monoubiquitination [#9, #7]. As a reader-writer module, YAF2 binds H2AK119ub1 and directs the YAF2-PRC1 complex to ubiquitinate H2A on neighboring nucleosomes, a positive-feedback mechanism that propagates the mark through cell division and is enhanced by histone H1-compacted chromatin [#0]. Sequence-specific targeting is achieved by bridging the transcription factor YY1 to PRC1: YAF2 binds the YY1 REPO domain and YY1 DNA binding is a prerequisite for Polycomb assembly at target loci [#1, #3]. YAF2 phosphorylation at Ser166 is required for efficient Ring1B-mediated H2A ubiquitination and target-gene repression, and loss of Yaf2 in embryonic stem cells compromises proliferation, perturbs differentiation, and de-represses lineage genes [#9, #12]. YAF2 and its paralog RYBP regulate largely distinct Polycomb target sets and have opposing effects on neural differentiation [#1, #12]. Beyond chromatin, YAF2 binds and differentially modulates MycN (activating) versus Myc (inhibitory) transcriptional activity [#5, #6], stabilizes PDCD5 to promote TP53-dependent apoptotic signaling under genotoxic stress [#8], and, when phosphorylated, stabilizes FANK1 to suppress apoptosis [#11].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established YAF2 as a Myc-family transcriptional cofactor by showing it binds the central region of nuclear MycN and enhances E-box-driven transactivation, framing an early non-chromatin function.\",\n      \"evidence\": \"Yeast two-hybrid, in vitro/in vivo binding, E-box reporter and MycN deletion mutagenesis\",\n      \"pmids\": [\"11593398\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which YAF2 boosts MycN activity unresolved\", \"No genome-wide MycN target validation\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Showed YAF2 interacts with hGABPβ and YY1 and positively regulates transcription, contrasting it functionally with RYBP and hinting at distinct paralog roles.\",\n      \"evidence\": \"Yeast two/three-hybrid, in vitro/in vivo binding, transcriptional reporter assays\",\n      \"pmids\": [\"11953439\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct chromatin occupancy not demonstrated\", \"Relationship of GABP activation to Polycomb function unclear\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Connected YAF2 to the Polycomb machinery by demonstrating its interaction with Ring1B/Ring1A, placing it within mammalian PcG complexes.\",\n      \"evidence\": \"Co-IP and colocalization in tissue culture, identification of splice isoforms\",\n      \"pmids\": [\"14557078\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Catalytic consequence of YAF2-Ring1B interaction not yet shown\", \"Target genes undefined\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Revealed opposing regulation within the Myc family by showing YAF2 inhibits Myc-mediated transactivation and transformation, unlike its activating effect on MycN.\",\n      \"evidence\": \"In vitro/in vivo binding, reporter and transformation assays\",\n      \"pmids\": [\"12706874\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis for opposite Myc vs MycN effects unknown\", \"In vivo relevance to tumorigenesis untested\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Demonstrated an essential survival function for YAF2 in vivo, as depletion in zebrafish triggers caspase 8-mediated apoptosis rescuable by human YAF2, establishing an anti-apoptotic role.\",\n      \"evidence\": \"Morpholino knockdown, caspase-inhibitor and mRNA rescue, apoptosis assays\",\n      \"pmids\": [\"16891308\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular link between YAF2 and caspase 8 not defined\", \"Relationship to Polycomb activity unaddressed\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Mapped sequence-specific Polycomb recruitment to the YY1 REPO domain–YAF2 interaction, showing YAF2 can recruit PcG proteins and repress transcription when tethered to DNA.\",\n      \"evidence\": \"Co-IP, REPO deletion mutagenesis, heterologous DNA-binding domain fusion repression, Drosophila dRYBP genetics\",\n      \"pmids\": [\"19960508\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Endogenous YY1-YAF2 target loci not enumerated\", \"Stoichiometry of bridging complex unknown\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Defined YAF2 as the obligate bridge between YY1 DNA binding and PRC1 recruitment and distinguished its target gene set from RYBP, clarifying paralog-specific Polycomb function.\",\n      \"evidence\": \"Reciprocal Co-IP, ChIP, YY1 knockdown/rescue, cross-species dRYBP complementation\",\n      \"pmids\": [\"24285299\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genome-wide map of YY1-dependent vs independent YAF2 targets incomplete\", \"How distinct YAF2 vs RYBP targeting is achieved unknown\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Identified a TP53-axis function: YAF2 binds and stabilizes PDCD5 against proteasomal degradation to promote TP53 activation during genotoxic stress.\",\n      \"evidence\": \"Yeast two-hybrid, Co-IP, siRNA, ubiquitination assays, etoposide stress, PDCD5 mutant rescue\",\n      \"pmids\": [\"25603536\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How YAF2 protects PDCD5 from ubiquitination mechanistically unclear\", \"Reconciliation with anti-apoptotic role not addressed\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Provided the integrated chromatin mechanism: YAF2 assembles into noncanonical PRC1 via residues 102–150 and its Ser166 phosphorylation is required for Ring1B-driven H2A ubiquitination, with Yaf2 loss in mESCs causing differentiation defects and gene de-repression.\",\n      \"evidence\": \"Co-IP, deletion and S166A mutagenesis, ChIP-seq, in vitro H2A ubiquitination, mESC knockout\",\n      \"pmids\": [\"29959227\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase responsible for Ser166 phosphorylation unidentified\", \"Structural detail of the 102–150 assembly region absent\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Established YAF2 as a reader-writer that propagates H2AK119ub1 through a positive-feedback loop, explaining heritable maintenance of the mark across cell division.\",\n      \"evidence\": \"Biochemical binding assays, chromatin fractionation, H1-compaction and cell division readouts, RYBP/YAF2-PRC1 disruption\",\n      \"pmids\": [\"32203418\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Quantitative contribution of YAF2 vs RYBP to propagation in vivo unclear\", \"How H1 compaction enhances distal spreading mechanistically undefined\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extended YAF2's adaptor role to chromatin-modifying deacetylation by showing it bridges YY1 and SIRT6 at 1:1:1 stoichiometry to accelerate H3K9 deacetylation and mitochondrial gene downregulation.\",\n      \"evidence\": \"Pulldown, cross-linking molar ratio, ChIP-qPCR, SIRT6 inhibition (tunicate model)\",\n      \"pmids\": [\"33875574\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Relevance to mammalian aging untested\", \"Independence from PRC1 function unclear\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Provided a phosphorylation-dependent anti-apoptotic mechanism: phospho-Ser167 YAF2 stabilizes polyubiquitinated FANK1 by binding its FN3 domain, suppressing tumor cell apoptosis.\",\n      \"evidence\": \"Co-IP, siRNA, proteasome inhibition, FN3/N-terminus domain mapping, phosphorylation and apoptosis assays\",\n      \"pmids\": [\"33784512\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Kinase and signaling input for Ser167 unknown\", \"Relationship between Ser166 (chromatin) and Ser167 (FANK1) phosphorylation events unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Resolved divergent paralog function in differentiation: Yaf2 loss redistributes RYBP and H2AK119ub onto co-targeted genes and promotes neural differentiation, opposite to Rybp loss, showing YAF2 restrains ectopic lineage gene activation.\",\n      \"evidence\": \"Rybp and Yaf2 KO mESCs, RYBP and H2AK119ub ChIP-seq, transcriptional profiling, neural differentiation assays\",\n      \"pmids\": [\"37935677\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism driving RYBP redistribution upon Yaf2 loss undefined\", \"Direct interplay with Wnt signaling not dissected for YAF2\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How YAF2's chromatin (vPRC1/H2AK119ub1) functions are mechanistically coordinated with its apoptosis-regulating roles (PDCD5/TP53 activation versus caspase 8 and FANK1-dependent survival), and which kinases control its functionally critical Ser166/Ser167 phosphorylation, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Upstream kinase for Ser166/167 unidentified\", \"No unified model reconciling pro- and anti-apoptotic activities\", \"No structural model of YAF2 in vPRC1 or its phospho-regulated states\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1, 3, 9, 10]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [2, 5, 6]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0140313\", \"supporting_discovery_ids\": [8, 11]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [5, 7]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [0, 9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 9, 12]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 3, 5, 6]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [4, 9, 12]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [4, 8, 11]}\n    ],\n    \"complexes\": [\"variant Polycomb Repressive Complex 1 (vPRC1)\"],\n    \"partners\": [\"RING1B\", \"YY1\", \"MYCN\", \"MYC\", \"PDCD5\", \"FANK1\", \"SIRT6\", \"GABPB1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}