{"gene":"YAF2","run_date":"2026-04-28T23:00:23","timeline":{"discoveries":[{"year":2020,"finding":"YAF2 specifically binds H2AK119ub1 to recruit 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 H2AK119ub1 by RYBP/YAF2-PRC1.","method":"Biochemical binding assays, in vitro ubiquitination assays, cell division inheritance experiments, disruption of RYBP/YAF2-PRC1 activity","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods (binding assay, catalytic assay, cell division propagation) in a single rigorous study, 91 citations","pmids":["32203418"],"is_preprint":false},{"year":2013,"finding":"YAF2 bridges the interaction between the transcription factor YY1 and the PRC1 complex, enabling PcG recruitment to DNA; YY1 DNA binding is required prior to YAF2-dependent PcG assembly on chromatin. Functional conservation demonstrated by rescue of Drosophila dRYBP mutants with mouse YAF2.","method":"Co-immunoprecipitation, ChIP assays in HeLa cells, YY1 knockdown, genetic rescue in Drosophila dRYBP mutants","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP, ChIP, genetic rescue across species, multiple labs confirmed interactions","pmids":["24285299"],"is_preprint":false},{"year":2010,"finding":"The YY1 REPO domain (25 amino acids) directly interacts with Yaf2, recruiting it to DNA; Yaf2 linked to a heterologous DNA-binding domain can recruit PcG proteins to DNA and mediate transcriptional repression; deletion of REPO domain abolishes interaction.","method":"Domain deletion analysis, heterologous DNA-binding domain fusion assay, transcriptional repression assays, Drosophila dRYBP mutation analysis","journal":"Journal of cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 — domain mapping plus functional assay, single lab","pmids":["19960508"],"is_preprint":false},{"year":2002,"finding":"YAF2 interacts with both hGABPβ and YY1 in vitro and in vivo; YAF2 positively regulates transcriptional activity of hGABP, while its paralog YEAF1 negatively regulates it; YEAF1 bridges hGABPβ and YY1 into a complex, as shown by yeast three-hybrid assay.","method":"Yeast two-hybrid screening, yeast three-hybrid assay, in vitro and in vivo binding assays, transcriptional activity assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods (two-hybrid, three-hybrid, in vitro and in vivo binding, transcriptional assay), single lab","pmids":["11953439"],"is_preprint":false},{"year":2015,"finding":"YAF2 binds PDCD5 and increases PDCD5 protein stability by inhibiting ubiquitin-dependent proteasomal degradation; upon genotoxic stress, YAF2 promotes TP53 activation via its association with PDCD5; YAF2 cannot promote TP53 activation without PDCD5.","method":"Yeast two-hybrid screen, Co-immunoprecipitation, ubiquitin-proteasome assays, siRNA knockdown, genotoxic stress response assays, PDCD5 deletion/mutation experiments","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods (Y2H, Co-IP, proteasome assay, KD), single lab","pmids":["25603536"],"is_preprint":false},{"year":2018,"finding":"Yaf2 assembles into a noncanonical PRC1 complex; residues 102-150 are required for this assembly. Serine 166 phosphorylation of Yaf2 is required for Ring1B-mediated H2A monoubiquitination and target gene repression; S166A mutation compromises these activities. Yaf2 deletion causes compromised proliferation and abnormal differentiation of mouse ESCs, with Yaf2 acting primarily as a transcriptional repressor for ectoderm-associated genes.","method":"Deletion analysis, phosphorylation site mutagenesis (S166A), genome-wide profiling, in vitro ubiquitination assays, mouse ESC differentiation assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 — reconstitution of ubiquitination activity, mutagenesis, genome-wide profiling, and differentiation phenotype in a single study","pmids":["29959227"],"is_preprint":false},{"year":2023,"finding":"RYBP and YAF2 have distinct regulatory functions in neural differentiation of ESCs: Rybp knockout impairs neural differentiation by activating Wnt signaling, while Yaf2 knockout promotes neural differentiation and leads to redistribution of RYBP binding and increased H2AK119ub enrichment on co-targeted genes.","method":"Knockout ESC lines, ChIP-seq, RNA-seq, neural differentiation assays, genome-wide profiling","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — clean KO with defined cellular phenotype and genome-wide profiling, two distinct KO lines with orthogonal readouts","pmids":["37935677"],"is_preprint":false},{"year":2001,"finding":"Yaf2 binds the central region of MycN in vitro and in vivo, co-localizes with MycN in 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-IP, nuclear localization (microscopy), E-box reporter transactivation assay, deletion analysis","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods (Y2H, in vitro, in vivo, reporter assay, deletion), single lab","pmids":["11593398"],"is_preprint":false},{"year":2003,"finding":"Yaf2 binds Myc protein in vivo and in vitro; in contrast to its activating effect on MycN, Yaf2 inhibits Myc-mediated transactivation and transformation.","method":"In vitro binding assay, in vivo Co-IP, transcriptional reporter assay, transformation assay","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 — in vitro and in vivo binding plus functional assays, single lab","pmids":["12706874"],"is_preprint":false},{"year":2003,"finding":"Mouse YAF2 protein interacts with Ring1B (and Ring1A), co-localizes with Ring1B in tissue culture cells, and is incorporated into PcG complexes; the YAF2 locus generates two distinct isoforms by alternative splicing.","method":"Biochemical pulldown, co-localization studies in tissue culture cells, alternative splicing analysis","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2-3 — Co-IP/pulldown plus colocalization, single lab","pmids":["14557078"],"is_preprint":false},{"year":2006,"finding":"Yaf2 functions as a survival factor during early zebrafish embryogenesis by inhibiting caspase 8-mediated apoptosis; depletion of zYaf2 activates widespread caspase 8-dependent apoptosis, which is rescued by human YAF2 mRNA or caspase 8-specific inhibitor.","method":"Morpholino knockdown in zebrafish, rescue with human YAF2 mRNA, pan-caspase and caspase 8-specific inhibitor treatment, apoptosis assays in cultured cells","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — morpholino KD with multiple rescue approaches (mRNA rescue, inhibitor rescue), single lab","pmids":["16891308"],"is_preprint":false},{"year":2021,"finding":"YAF2 mediates the interaction between YY1 and SIRT6; YAF2 bridges YY1 and SIRT6 with a 1:1:1 molar ratio, and this complex promotes SIRT6-dependent H3K9 deacetylation at the TFAM gene promoter, leading to aging-related mitochondrial downregulation in tunicates.","method":"Pulldown assays, protein cross-linking, ChIP-qPCR, mRNA co-transfection experiments, SIRT6 inhibitor treatment","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 — pulldown, cross-linking stoichiometry, ChIP-qPCR, functional rescue, single lab with tunicate model","pmids":["33875574"],"is_preprint":false},{"year":2021,"finding":"Phosphorylated YAF2 (at Serine 167) inhibits proteasomal degradation of polyubiquitinated FANK1 by binding to it (FN3 domain of FANK1 binds N-terminus of YAF2), thereby stabilizing FANK1 and suppressing tumor cell apoptosis in a FANK1-dependent manner.","method":"Co-immunoprecipitation, siRNA knockdown, proteasome inhibitor assays, domain mapping, apoptosis assays","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2-3 — Co-IP with domain mapping, KD with functional readout, single lab","pmids":["33784512"],"is_preprint":false}],"current_model":"YAF2 is a component of variant PRC1 complexes (vPRC1) that binds H2AK119ub1 via a positive-feedback mechanism to catalyze and propagate H2A monoubiquitination on neighboring nucleosomes; it bridges YY1 (via the REPO domain) to PRC1, enabling DNA-targeted Polycomb repression, and its phosphorylation status (Ser166/167) regulates Ring1B-mediated H2A ubiquitination, FANK1 stability, and apoptosis; additionally, YAF2 modulates transcription factor activity (hGABP, MycN, Myc, YY1-SIRT6) and stabilizes PDCD5 to promote TP53-dependent apoptotic responses to genotoxic stress."},"narrative":{"teleology":[{"year":2001,"claim":"Identifying YAF2 as a nuclear cofactor of MycN established its first role in transcriptional regulation, showing it could directly bind and enhance MycN transactivation from E-box elements.","evidence":"Yeast two-hybrid, Co-IP, nuclear co-localization, E-box reporter assays with deletion mapping","pmids":["11593398"],"confidence":"Medium","gaps":["Endogenous target genes of the YAF2–MycN interaction not identified","Physiological relevance in neuroblastoma not tested in vivo"]},{"year":2002,"claim":"Demonstrating that YAF2 interacts with both hGABPβ and YY1 and positively regulates hGABP transcriptional activity revealed YAF2 as a modular transcription factor cofactor with partner-dependent activating or repressing effects.","evidence":"Yeast two-hybrid, yeast three-hybrid, in vitro/in vivo binding, transcriptional activity assays","pmids":["11953439"],"confidence":"Medium","gaps":["Chromatin-level targets of hGABP–YAF2 not mapped","Structural basis of differential regulation versus YEAF1 unknown"]},{"year":2003,"claim":"Finding that YAF2 inhibits Myc transactivation and transformation—opposite to its enhancement of MycN—established context-dependent transcriptional modulation by YAF2, while concurrent discovery of YAF2 incorporation into Ring1B-containing PcG complexes connected it to Polycomb biology.","evidence":"Co-IP, reporter and transformation assays (Myc); biochemical pulldown and co-localization with Ring1B in tissue culture cells","pmids":["12706874","14557078"],"confidence":"Medium","gaps":["Molecular basis for opposite effects on Myc versus MycN not determined","Composition of the YAF2-containing PcG complex not fully defined"]},{"year":2006,"claim":"Zebrafish morpholino studies revealed a developmental survival function for Yaf2, showing it suppresses caspase 8-mediated apoptosis during embryogenesis—a role conserved across vertebrates as demonstrated by rescue with human YAF2.","evidence":"Morpholino knockdown in zebrafish embryos, rescue with human YAF2 mRNA and caspase 8 inhibitor","pmids":["16891308"],"confidence":"Medium","gaps":["Mechanism by which YAF2 inhibits caspase 8 activation not elucidated","Morpholino approach carries off-target risk; genetic knockout not performed"]},{"year":2010,"claim":"Mapping the YY1 REPO domain as the minimal 25-amino-acid element sufficient for YAF2 recruitment, and showing that YAF2 fused to a heterologous DNA-binding domain recruits PcG and mediates repression, established the molecular logic of YY1-directed Polycomb targeting through YAF2.","evidence":"Domain deletion, heterologous DBD fusion, transcriptional repression assays, Drosophila dRYBP analysis","pmids":["19960508"],"confidence":"Medium","gaps":["Structure of the REPO–YAF2 interface not resolved","Whether all YY1-bound sites recruit PcG via YAF2 in vivo was untested"]},{"year":2013,"claim":"ChIP experiments and cross-species genetic rescue demonstrated that YAF2 bridges YY1 to PRC1 on chromatin in vivo, with YY1 DNA binding required prior to YAF2-dependent PcG assembly, establishing the order of events in DNA-targeted Polycomb recruitment.","evidence":"Co-IP, ChIP in HeLa cells, YY1 knockdown, rescue of Drosophila dRYBP mutants with mouse YAF2","pmids":["24285299"],"confidence":"High","gaps":["Genome-wide sites of YY1–YAF2–PRC1 co-occupancy not profiled at this stage","Whether YAF2 is required at all PRC1 target loci or a subset unclear"]},{"year":2015,"claim":"Discovery that YAF2 stabilizes PDCD5 by blocking its ubiquitin-dependent proteasomal degradation, and that this is required for TP53 activation upon genotoxic stress, revealed a non-chromatin function for YAF2 in apoptotic signaling.","evidence":"Yeast two-hybrid, Co-IP, ubiquitin-proteasome assays, siRNA knockdown, genotoxic stress response assays","pmids":["25603536"],"confidence":"Medium","gaps":["E3 ligase targeting PDCD5 that YAF2 antagonizes not identified","In vivo validation of this apoptotic axis lacking"]},{"year":2018,"claim":"Reconstitution and mutagenesis demonstrated that Ser166 phosphorylation is required for Ring1B-mediated H2A ubiquitination and that residues 102–150 mediate PRC1 assembly; Yaf2 deletion in mouse ESCs caused proliferation defects and aberrant ectoderm gene derepression, establishing YAF2 as a functional noncanonical PRC1 subunit controlling differentiation.","evidence":"Phosphosite mutagenesis (S166A), in vitro ubiquitination, genome-wide profiling, mouse ESC differentiation assays","pmids":["29959227"],"confidence":"High","gaps":["Kinase responsible for Ser166 phosphorylation not identified","Whether phosphorylation is dynamically regulated during differentiation not tested"]},{"year":2020,"claim":"Biochemical reconstitution showed that YAF2 (and its paralog RYBP) directly reads H2AK119ub1 to recruit variant PRC1, which then ubiquitinates H2A on neighboring nucleosomes, establishing a positive-feedback loop for Polycomb mark propagation through cell division; histone H1-compacted chromatin enhances distal spreading.","evidence":"Binding assays, in vitro ubiquitination on nucleosome substrates, cell division inheritance experiments","pmids":["32203418"],"confidence":"High","gaps":["Relative contributions of YAF2 versus RYBP to propagation in vivo not separated","Whether the feedback is self-limiting or requires additional regulation not addressed"]},{"year":2021,"claim":"Two independent studies expanded YAF2's scaffolding repertoire: one showed YAF2 bridges YY1 and SIRT6 (1:1:1) to drive H3K9 deacetylation at the TFAM promoter during aging; the other showed phospho-Ser167 YAF2 stabilizes FANK1 against proteasomal degradation to suppress tumor cell apoptosis.","evidence":"Pulldown/cross-linking stoichiometry, ChIP-qPCR in tunicate model (YY1–SIRT6); Co-IP, domain mapping, apoptosis assays in tumor cells (FANK1)","pmids":["33875574","33784512"],"confidence":"Medium","gaps":["YY1–YAF2–SIRT6 axis validated only in tunicate; conservation in mammals not shown","Kinase for Ser167 not identified; relationship to Ser166 phosphorylation in PRC1 context unclear"]},{"year":2023,"claim":"Knockout comparisons in ESCs showed that YAF2 and RYBP are not redundant: Yaf2 loss promotes neural differentiation and causes RYBP redistribution with increased H2AK119ub at co-targeted genes, establishing paralog-specific and antagonistic roles in lineage decisions.","evidence":"Yaf2 and Rybp knockout ESC lines, ChIP-seq, RNA-seq, neural differentiation assays","pmids":["37935677"],"confidence":"High","gaps":["Mechanism by which YAF2 loss leads to RYBP redistribution rather than simple loss of PRC1 occupancy not elucidated","In vivo developmental phenotypes of Yaf2 knockout mice not reported"]},{"year":null,"claim":"Key unresolved questions include the identity of the kinase(s) phosphorylating YAF2 at Ser166/167, the structural basis of YAF2's recognition of H2AK119ub1, how the chromatin (PRC1) and non-chromatin (PDCD5/FANK1/apoptosis) functions are coordinated, and the in vivo developmental consequences of YAF2 loss in mammals.","evidence":"","pmids":[],"confidence":"Low","gaps":["No kinase identified for Ser166/167 phosphorylation","No crystal or cryo-EM structure of YAF2 in any complex","No conditional knockout mouse phenotype reported"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[0,5]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,2,11]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[3,7,8]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4,12]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1,5,7,9]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0,1,5]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,1,5,6]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[2,3,5,7,8]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[4,10,12]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[5,6]}],"complexes":["variant PRC1 (noncanonical PRC1)","YY1-YAF2-SIRT6 complex"],"partners":["RING1B","YY1","RYBP","PDCD5","FANK1","MYCN","MYC","SIRT6"],"other_free_text":[]},"mechanistic_narrative":"YAF2 is a Polycomb group (PcG) cofactor that functions as a scaffold within variant PRC1 complexes to propagate histone H2A monoubiquitination and modulate transcription factor activity. YAF2 specifically recognizes H2AK119ub1 and, as a subunit of noncanonical PRC1 (with Ring1B), catalyzes ubiquitination of H2A on neighboring nucleosomes through a positive-feedback mechanism that maintains Polycomb repression through cell division; serine 166 phosphorylation of YAF2 is required for Ring1B-mediated H2A ubiquitination and target gene repression, and Yaf2 loss in ESCs compromises proliferation and alters differentiation fate [PMID:32203418, PMID:29959227, PMID:37935677]. YAF2 bridges YY1 to PRC1 via the YY1 REPO domain, enabling DNA-targeted Polycomb recruitment, and also bridges YY1 to SIRT6 to promote H3K9 deacetylation at specific promoters [PMID:24285299, PMID:19960508, PMID:33875574]. Beyond chromatin regulation, YAF2 modulates transcription factor output—enhancing MycN- and hGABP-mediated transactivation while inhibiting Myc-mediated transactivation and transformation—and stabilizes PDCD5 to promote TP53-dependent apoptosis under genotoxic stress, while phosphorylated YAF2 stabilizes FANK1 to suppress apoptosis in tumor cells [PMID:11593398, PMID:12706874, PMID:25603536, PMID:33784512]."},"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":91,"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":52,"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 transcription factors.","date":"2002","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11953439","citation_count":50,"is_preprint":false},{"pmid":"19960508","id":"PMC_19960508","title":"PcG recruitment by the YY1 REPO domain can be mediated by Yaf2.","date":"2010","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19960508","citation_count":42,"is_preprint":false},{"pmid":"32950105","id":"PMC_32950105","title":"TV-circRGPD6 Nanoparticle Suppresses Breast Cancer Stem Cell-Mediated Metastasis via the miR-26b/YAF2 Axis.","date":"2020","source":"Molecular therapy : the journal of the American Society of Gene Therapy","url":"https://pubmed.ncbi.nlm.nih.gov/32950105","citation_count":29,"is_preprint":false},{"pmid":"16891308","id":"PMC_16891308","title":"Yaf2 inhibits caspase 8-mediated apoptosis and regulates cell survival during zebrafish embryogenesis.","date":"2006","source":"The Journal of biological 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pyroptosis in a cell model of Parkinson's disease via targeting miR-5047/YAF2 signaling.","date":"2023","source":"Immunity, inflammation and disease","url":"https://pubmed.ncbi.nlm.nih.gov/37382256","citation_count":4,"is_preprint":false},{"pmid":"39065263","id":"PMC_39065263","title":"Exosomal miR-7-25207 Increases Subgroup J Avian Leukosis Virus Titers by Targeting the Akt-CyclinQ1 and PRC1-YAF2 Dual Pathways.","date":"2024","source":"Microorganisms","url":"https://pubmed.ncbi.nlm.nih.gov/39065263","citation_count":0,"is_preprint":false},{"pmid":"40432551","id":"PMC_40432551","title":"RETRACTION: NEAT1 Enhances MPP + -Induced Pyroptosis in a Cell Model of Parkinson's Disease via Targeting miR-5047/YAF2 Signaling.","date":"2025","source":"Immunity, inflammation and disease","url":"https://pubmed.ncbi.nlm.nih.gov/40432551","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11777,"output_tokens":3165,"usd":0.041403},"stage2":{"model":"claude-opus-4-6","input_tokens":6534,"output_tokens":3370,"usd":0.17538},"total_usd":0.216783,"stage1_batch_id":"msgbatch_01BparvgRZ9S2LMidvaoo86K","stage2_batch_id":"msgbatch_01NkBfv9SVZWthhS7j6mU6G3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"YAF2 specifically binds H2AK119ub1 to recruit 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 H2AK119ub1 by RYBP/YAF2-PRC1.\",\n      \"method\": \"Biochemical binding assays, in vitro ubiquitination assays, cell division inheritance experiments, disruption of RYBP/YAF2-PRC1 activity\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods (binding assay, catalytic assay, cell division propagation) in a single rigorous study, 91 citations\",\n      \"pmids\": [\"32203418\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"YAF2 bridges the interaction between the transcription factor YY1 and the PRC1 complex, enabling PcG recruitment to DNA; YY1 DNA binding is required prior to YAF2-dependent PcG assembly on chromatin. Functional conservation demonstrated by rescue of Drosophila dRYBP mutants with mouse YAF2.\",\n      \"method\": \"Co-immunoprecipitation, ChIP assays in HeLa cells, YY1 knockdown, genetic rescue in Drosophila dRYBP mutants\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, ChIP, genetic rescue across species, multiple labs confirmed interactions\",\n      \"pmids\": [\"24285299\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The YY1 REPO domain (25 amino acids) directly interacts with Yaf2, recruiting it to DNA; Yaf2 linked to a heterologous DNA-binding domain can recruit PcG proteins to DNA and mediate transcriptional repression; deletion of REPO domain abolishes interaction.\",\n      \"method\": \"Domain deletion analysis, heterologous DNA-binding domain fusion assay, transcriptional repression assays, Drosophila dRYBP mutation analysis\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — domain mapping plus functional assay, single lab\",\n      \"pmids\": [\"19960508\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"YAF2 interacts with both hGABPβ and YY1 in vitro and in vivo; YAF2 positively regulates transcriptional activity of hGABP, while its paralog YEAF1 negatively regulates it; YEAF1 bridges hGABPβ and YY1 into a complex, as shown by yeast three-hybrid assay.\",\n      \"method\": \"Yeast two-hybrid screening, yeast three-hybrid assay, in vitro and in vivo binding assays, transcriptional activity assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (two-hybrid, three-hybrid, in vitro and in vivo binding, transcriptional assay), single lab\",\n      \"pmids\": [\"11953439\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"YAF2 binds PDCD5 and increases PDCD5 protein stability by inhibiting ubiquitin-dependent proteasomal degradation; upon genotoxic stress, YAF2 promotes TP53 activation via its association with PDCD5; YAF2 cannot promote TP53 activation without PDCD5.\",\n      \"method\": \"Yeast two-hybrid screen, Co-immunoprecipitation, ubiquitin-proteasome assays, siRNA knockdown, genotoxic stress response assays, PDCD5 deletion/mutation experiments\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (Y2H, Co-IP, proteasome assay, KD), single lab\",\n      \"pmids\": [\"25603536\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Yaf2 assembles into a noncanonical PRC1 complex; residues 102-150 are required for this assembly. Serine 166 phosphorylation of Yaf2 is required for Ring1B-mediated H2A monoubiquitination and target gene repression; S166A mutation compromises these activities. Yaf2 deletion causes compromised proliferation and abnormal differentiation of mouse ESCs, with Yaf2 acting primarily as a transcriptional repressor for ectoderm-associated genes.\",\n      \"method\": \"Deletion analysis, phosphorylation site mutagenesis (S166A), genome-wide profiling, in vitro ubiquitination assays, mouse ESC differentiation assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — reconstitution of ubiquitination activity, mutagenesis, genome-wide profiling, and differentiation phenotype in a single study\",\n      \"pmids\": [\"29959227\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RYBP and YAF2 have distinct regulatory functions in neural differentiation of ESCs: Rybp knockout impairs neural differentiation by activating Wnt signaling, while Yaf2 knockout promotes neural differentiation and leads to redistribution of RYBP binding and increased H2AK119ub enrichment on co-targeted genes.\",\n      \"method\": \"Knockout ESC lines, ChIP-seq, RNA-seq, neural differentiation assays, genome-wide profiling\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined cellular phenotype and genome-wide profiling, two distinct KO lines with orthogonal readouts\",\n      \"pmids\": [\"37935677\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Yaf2 binds the central region of MycN in vitro and in vivo, co-localizes with MycN in 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-IP, nuclear localization (microscopy), E-box reporter transactivation assay, deletion analysis\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (Y2H, in vitro, in vivo, reporter assay, deletion), single lab\",\n      \"pmids\": [\"11593398\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Yaf2 binds Myc protein in vivo and in vitro; in contrast to its activating effect on MycN, Yaf2 inhibits Myc-mediated transactivation and transformation.\",\n      \"method\": \"In vitro binding assay, in vivo Co-IP, transcriptional reporter assay, transformation assay\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vitro and in vivo binding plus functional assays, single lab\",\n      \"pmids\": [\"12706874\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Mouse YAF2 protein interacts with Ring1B (and Ring1A), co-localizes with Ring1B in tissue culture cells, and is incorporated into PcG complexes; the YAF2 locus generates two distinct isoforms by alternative splicing.\",\n      \"method\": \"Biochemical pulldown, co-localization studies in tissue culture cells, alternative splicing analysis\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — Co-IP/pulldown plus colocalization, single lab\",\n      \"pmids\": [\"14557078\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Yaf2 functions as a survival factor during early zebrafish embryogenesis by inhibiting caspase 8-mediated apoptosis; depletion of zYaf2 activates widespread caspase 8-dependent apoptosis, which is rescued by human YAF2 mRNA or caspase 8-specific inhibitor.\",\n      \"method\": \"Morpholino knockdown in zebrafish, rescue with human YAF2 mRNA, pan-caspase and caspase 8-specific inhibitor treatment, apoptosis assays in cultured cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — morpholino KD with multiple rescue approaches (mRNA rescue, inhibitor rescue), single lab\",\n      \"pmids\": [\"16891308\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"YAF2 mediates the interaction between YY1 and SIRT6; YAF2 bridges YY1 and SIRT6 with a 1:1:1 molar ratio, and this complex promotes SIRT6-dependent H3K9 deacetylation at the TFAM gene promoter, leading to aging-related mitochondrial downregulation in tunicates.\",\n      \"method\": \"Pulldown assays, protein cross-linking, ChIP-qPCR, mRNA co-transfection experiments, SIRT6 inhibitor treatment\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — pulldown, cross-linking stoichiometry, ChIP-qPCR, functional rescue, single lab with 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 it (FN3 domain of FANK1 binds N-terminus of YAF2), thereby stabilizing FANK1 and suppressing tumor cell apoptosis in a FANK1-dependent manner.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, proteasome inhibitor assays, domain mapping, apoptosis assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — Co-IP with domain mapping, KD with functional readout, single lab\",\n      \"pmids\": [\"33784512\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"YAF2 is a component of variant PRC1 complexes (vPRC1) that binds H2AK119ub1 via a positive-feedback mechanism to catalyze and propagate H2A monoubiquitination on neighboring nucleosomes; it bridges YY1 (via the REPO domain) to PRC1, enabling DNA-targeted Polycomb repression, and its phosphorylation status (Ser166/167) regulates Ring1B-mediated H2A ubiquitination, FANK1 stability, and apoptosis; additionally, YAF2 modulates transcription factor activity (hGABP, MycN, Myc, YY1-SIRT6) and stabilizes PDCD5 to promote TP53-dependent apoptotic responses to genotoxic stress.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"YAF2 is a Polycomb group (PcG) cofactor that functions as a scaffold within variant PRC1 complexes to propagate histone H2A monoubiquitination and modulate transcription factor activity. YAF2 specifically recognizes H2AK119ub1 and, as a subunit of noncanonical PRC1 (with Ring1B), catalyzes ubiquitination of H2A on neighboring nucleosomes through a positive-feedback mechanism that maintains Polycomb repression through cell division; serine 166 phosphorylation of YAF2 is required for Ring1B-mediated H2A ubiquitination and target gene repression, and Yaf2 loss in ESCs compromises proliferation and alters differentiation fate [PMID:32203418, PMID:29959227, PMID:37935677]. YAF2 bridges YY1 to PRC1 via the YY1 REPO domain, enabling DNA-targeted Polycomb recruitment, and also bridges YY1 to SIRT6 to promote H3K9 deacetylation at specific promoters [PMID:24285299, PMID:19960508, PMID:33875574]. Beyond chromatin regulation, YAF2 modulates transcription factor output—enhancing MycN- and hGABP-mediated transactivation while inhibiting Myc-mediated transactivation and transformation—and stabilizes PDCD5 to promote TP53-dependent apoptosis under genotoxic stress, while phosphorylated YAF2 stabilizes FANK1 to suppress apoptosis in tumor cells [PMID:11593398, PMID:12706874, PMID:25603536, PMID:33784512].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Identifying YAF2 as a nuclear cofactor of MycN established its first role in transcriptional regulation, showing it could directly bind and enhance MycN transactivation from E-box elements.\",\n      \"evidence\": \"Yeast two-hybrid, Co-IP, nuclear co-localization, E-box reporter assays with deletion mapping\",\n      \"pmids\": [\"11593398\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Endogenous target genes of the YAF2–MycN interaction not identified\", \"Physiological relevance in neuroblastoma not tested in vivo\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Demonstrating that YAF2 interacts with both hGABPβ and YY1 and positively regulates hGABP transcriptional activity revealed YAF2 as a modular transcription factor cofactor with partner-dependent activating or repressing effects.\",\n      \"evidence\": \"Yeast two-hybrid, yeast three-hybrid, in vitro/in vivo binding, transcriptional activity assays\",\n      \"pmids\": [\"11953439\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Chromatin-level targets of hGABP–YAF2 not mapped\", \"Structural basis of differential regulation versus YEAF1 unknown\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Finding that YAF2 inhibits Myc transactivation and transformation—opposite to its enhancement of MycN—established context-dependent transcriptional modulation by YAF2, while concurrent discovery of YAF2 incorporation into Ring1B-containing PcG complexes connected it to Polycomb biology.\",\n      \"evidence\": \"Co-IP, reporter and transformation assays (Myc); biochemical pulldown and co-localization with Ring1B in tissue culture cells\",\n      \"pmids\": [\"12706874\", \"14557078\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis for opposite effects on Myc versus MycN not determined\", \"Composition of the YAF2-containing PcG complex not fully defined\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Zebrafish morpholino studies revealed a developmental survival function for Yaf2, showing it suppresses caspase 8-mediated apoptosis during embryogenesis—a role conserved across vertebrates as demonstrated by rescue with human YAF2.\",\n      \"evidence\": \"Morpholino knockdown in zebrafish embryos, rescue with human YAF2 mRNA and caspase 8 inhibitor\",\n      \"pmids\": [\"16891308\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which YAF2 inhibits caspase 8 activation not elucidated\", \"Morpholino approach carries off-target risk; genetic knockout not performed\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Mapping the YY1 REPO domain as the minimal 25-amino-acid element sufficient for YAF2 recruitment, and showing that YAF2 fused to a heterologous DNA-binding domain recruits PcG and mediates repression, established the molecular logic of YY1-directed Polycomb targeting through YAF2.\",\n      \"evidence\": \"Domain deletion, heterologous DBD fusion, transcriptional repression assays, Drosophila dRYBP analysis\",\n      \"pmids\": [\"19960508\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structure of the REPO–YAF2 interface not resolved\", \"Whether all YY1-bound sites recruit PcG via YAF2 in vivo was untested\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"ChIP experiments and cross-species genetic rescue demonstrated that YAF2 bridges YY1 to PRC1 on chromatin in vivo, with YY1 DNA binding required prior to YAF2-dependent PcG assembly, establishing the order of events in DNA-targeted Polycomb recruitment.\",\n      \"evidence\": \"Co-IP, ChIP in HeLa cells, YY1 knockdown, rescue of Drosophila dRYBP mutants with mouse YAF2\",\n      \"pmids\": [\"24285299\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genome-wide sites of YY1–YAF2–PRC1 co-occupancy not profiled at this stage\", \"Whether YAF2 is required at all PRC1 target loci or a subset unclear\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Discovery that YAF2 stabilizes PDCD5 by blocking its ubiquitin-dependent proteasomal degradation, and that this is required for TP53 activation upon genotoxic stress, revealed a non-chromatin function for YAF2 in apoptotic signaling.\",\n      \"evidence\": \"Yeast two-hybrid, Co-IP, ubiquitin-proteasome assays, siRNA knockdown, genotoxic stress response assays\",\n      \"pmids\": [\"25603536\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"E3 ligase targeting PDCD5 that YAF2 antagonizes not identified\", \"In vivo validation of this apoptotic axis lacking\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Reconstitution and mutagenesis demonstrated that Ser166 phosphorylation is required for Ring1B-mediated H2A ubiquitination and that residues 102–150 mediate PRC1 assembly; Yaf2 deletion in mouse ESCs caused proliferation defects and aberrant ectoderm gene derepression, establishing YAF2 as a functional noncanonical PRC1 subunit controlling differentiation.\",\n      \"evidence\": \"Phosphosite mutagenesis (S166A), in vitro ubiquitination, genome-wide profiling, mouse ESC differentiation assays\",\n      \"pmids\": [\"29959227\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase responsible for Ser166 phosphorylation not identified\", \"Whether phosphorylation is dynamically regulated during differentiation not tested\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Biochemical reconstitution showed that YAF2 (and its paralog RYBP) directly reads H2AK119ub1 to recruit variant PRC1, which then ubiquitinates H2A on neighboring nucleosomes, establishing a positive-feedback loop for Polycomb mark propagation through cell division; histone H1-compacted chromatin enhances distal spreading.\",\n      \"evidence\": \"Binding assays, in vitro ubiquitination on nucleosome substrates, cell division inheritance experiments\",\n      \"pmids\": [\"32203418\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative contributions of YAF2 versus RYBP to propagation in vivo not separated\", \"Whether the feedback is self-limiting or requires additional regulation not addressed\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Two independent studies expanded YAF2's scaffolding repertoire: one showed YAF2 bridges YY1 and SIRT6 (1:1:1) to drive H3K9 deacetylation at the TFAM promoter during aging; the other showed phospho-Ser167 YAF2 stabilizes FANK1 against proteasomal degradation to suppress tumor cell apoptosis.\",\n      \"evidence\": \"Pulldown/cross-linking stoichiometry, ChIP-qPCR in tunicate model (YY1–SIRT6); Co-IP, domain mapping, apoptosis assays in tumor cells (FANK1)\",\n      \"pmids\": [\"33875574\", \"33784512\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"YY1–YAF2–SIRT6 axis validated only in tunicate; conservation in mammals not shown\", \"Kinase for Ser167 not identified; relationship to Ser166 phosphorylation in PRC1 context unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Knockout comparisons in ESCs showed that YAF2 and RYBP are not redundant: Yaf2 loss promotes neural differentiation and causes RYBP redistribution with increased H2AK119ub at co-targeted genes, establishing paralog-specific and antagonistic roles in lineage decisions.\",\n      \"evidence\": \"Yaf2 and Rybp knockout ESC lines, ChIP-seq, RNA-seq, neural differentiation assays\",\n      \"pmids\": [\"37935677\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which YAF2 loss leads to RYBP redistribution rather than simple loss of PRC1 occupancy not elucidated\", \"In vivo developmental phenotypes of Yaf2 knockout mice not reported\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the identity of the kinase(s) phosphorylating YAF2 at Ser166/167, the structural basis of YAF2's recognition of H2AK119ub1, how the chromatin (PRC1) and non-chromatin (PDCD5/FANK1/apoptosis) functions are coordinated, and the in vivo developmental consequences of YAF2 loss in mammals.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No kinase identified for Ser166/167 phosphorylation\", \"No crystal or cryo-EM structure of YAF2 in any complex\", \"No conditional knockout mouse phenotype reported\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 2, 11]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [3, 7, 8]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4, 12]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 5, 7, 9]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0, 1, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 1, 5, 6]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [2, 3, 5, 7, 8]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [4, 10, 12]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [5, 6]}\n    ],\n    \"complexes\": [\n      \"variant PRC1 (noncanonical PRC1)\",\n      \"YY1-YAF2-SIRT6 complex\"\n    ],\n    \"partners\": [\n      \"RING1B\",\n      \"YY1\",\n      \"RYBP\",\n      \"PDCD5\",\n      \"FANK1\",\n      \"MYCN\",\n      \"MYC\",\n      \"SIRT6\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}