{"gene":"MTF2","run_date":"2026-06-10T02:59:51","timeline":{"discoveries":[{"year":2018,"finding":"MTF2 directly binds DNA in a methylation-sensitive manner, selectively recognizing regions with high density of unmethylated CpGs in a context of reduced helix twist, and is essential for genome-wide recruitment of the PRC2 catalytic subunit EZH2 to target genes in mouse embryonic stem cells; MTF2 knockout abolishes EZH2 recruitment and greatly reduces H3K27me3 deposition.","method":"MTF2 knockout ESCs, ChIP-seq for EZH2 and H3K27me3, in vitro DNA binding assays, genome-wide analysis of CpG methylation and helix twist","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (KO, ChIP-seq, in vitro binding), replicated in both in vitro and in vivo contexts in a single rigorous study","pmids":["29808031"],"is_preprint":false},{"year":2011,"finding":"MTF2 is a component of the PRC2 complex in mouse ES cells and, together with JARID2 and esPRC2p48, synergistically stimulates the histone methyltransferase activity of PRC2 in vitro; knockdown of MTF2 alters H3K27 methylation levels and causes expression of differentiation-associated genes.","method":"Co-immunoprecipitation, in vitro histone methyltransferase assay with reconstituted PRC2 complex, siRNA knockdown in ES cells, gene expression analysis","journal":"Stem cells (Dayton, Ohio)","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro enzymatic reconstitution assay combined with Co-IP and functional KD, single lab but multiple orthogonal methods","pmids":["21732481"],"is_preprint":false},{"year":2010,"finding":"Pcl2/Mtf2 forms a complex with PRC2 and binds to Hox gene loci in a PRC2-dependent manner; it is required for PRC2-mediated Hox gene repression and exhibits a synergistic effect on PRC1-mediated Hox repression without major alterations in H3K27me3 or PRC1 deposition; paradoxically, in embryonic fibroblasts Pcl2 activates Cdkn2a expression by locally suppressing PRC2 catalytic activity.","method":"Co-immunoprecipitation, ChIP, conditional knockout and knockdown mouse genetics, gene expression analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, ChIP, in vivo genetic models, multiple orthogonal methods","pmids":["21059868"],"is_preprint":false},{"year":2004,"finding":"Chick Pcl2 (ortholog of MTF2) functions as a transcriptional repressor through its PHD finger domain; it directly interacts with EZH2 (a PRC2 component) via pulldown assay, represses Shh promoter activity in vitro, and regulates left-right axis patterning in chick embryos by silencing Shh expression in the right side of Hensen's node.","method":"In vitro pulldown assay (PHD finger–EZH2 interaction), in vitro transcription repression mapping, gain- and loss-of-function in chick embryos, luciferase reporter assay for Shh promoter","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — direct binding demonstrated by pulldown, functional domain mapping, in vivo rescue, multiple orthogonal assays in single study","pmids":["15294861"],"is_preprint":false},{"year":2018,"finding":"MTF2-PRC2 directly represses MDM2 in hematopoietic cells; loss of MTF2 results in overexpression of MDM2, which inhibits p53, leading to defects in cell-cycle regulation and apoptosis and chemoresistance in AML; overexpression of MTF2 or MDM2 inhibitors restored p53 activity and chemosensitivity.","method":"MTF2 overexpression/knockdown in CD34+CD38- AML cells, ChIP-seq, patient-derived xenograft mouse model, MDM2 inhibitor treatment, gene expression and apoptosis assays","journal":"Cancer discovery","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP-seq evidence of direct repression, in vivo PDX model, functional rescue, single lab","pmids":["30115703"],"is_preprint":false},{"year":2018,"finding":"Mtf2 is required for maintenance of core PRC2 protein levels and global H3K27me3 at promoter-proximal regions in erythroid progenitors; Mtf2-knockout embryos show global loss of H3K27me3, de-repression of canonical Wnt signaling, and die by e15.5 due to severe anemia; chemical inhibition of Wnt signaling rescued Mtf2-deficient erythroblast differentiation in vitro.","method":"Conditional Mtf2 knockout mice, ChIP-seq for H3K27me3, Western blot for PRC2 core proteins, gene regulatory network analysis, chemical Wnt inhibitor rescue in vitro","journal":"Cell discovery","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo KO with defined phenotype, ChIP-seq, protein level analysis, pathway-specific rescue, multiple orthogonal methods","pmids":["29736258"],"is_preprint":false},{"year":2011,"finding":"PCL2 depletion in ESCs leads to decreased H3K27me3 at promoters of pluripotency transcription factors Tbx3, Klf4, and Foxd3, with concomitant upregulation of these genes, which subsequently activate Oct4, Nanog, and Sox2 through a feed-forward circuit, increasing self-renewal and delaying differentiation.","method":"siRNA knockdown in mouse ESCs, ChIP for H3K27me3 at specific promoters, gene expression analysis, flow cytometry for pluripotency markers","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP at specific loci combined with gene expression changes and functional phenotype, single lab","pmids":["21193838"],"is_preprint":false},{"year":2025,"finding":"MTF2 stimulates PRC2 histone methyltransferase (HMT) activity in vitro using reconstituted substrates; MTF2 promotes PRC2 chromatin-binding activity in a DNA-sequence-dependent manner (GCN-rich sequences); MTF2 together with JARID2 and EPOP fosters PRC2-mediated H3K27me3 deposition at chromatin nucleation sites.","method":"In vitro HMT assay with reconstituted PRC2, binding assays with reconstituted dinucleosome substrates, EED-rescue system in vivo for chromatin recruitment","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution assay with defined substrates and in vivo EED-rescue system, multiple orthogonal approaches in single study","pmids":["41650228"],"is_preprint":false},{"year":2018,"finding":"PCL2 protects p53 from MDM2-mediated ubiquitination and degradation by sequestering MDM2 into the nucleolus, thereby elevating p53 protein stability and increasing expression of p53 target genes in breast cancer cells.","method":"PCL2 overexpression and knockdown in breast cancer cells, co-immunoprecipitation, ubiquitination assay, Western blot, subcellular fractionation/immunofluorescence for MDM2 nucleolar localization","journal":"Science bulletin","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, ubiquitination assay, subcellular localization experiment with functional consequence, single lab","pmids":["36658883"],"is_preprint":false},{"year":2024,"finding":"MTF2 directly binds to EZH2 in osteosarcoma cells and promotes EZH2-mediated silencing of SFRP1, thereby activating Wnt signaling to drive osteosarcoma progression; EZH2 upregulation or SFRP1 antagonism counteracted effects of MTF2 knockdown.","method":"Co-immunoprecipitation (Co-IP) assay for MTF2-EZH2 interaction, siRNA knockdown, Western blot, cell proliferation/invasion/apoptosis assays, rescue experiments","journal":"Journal of orthopaedic surgery and research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP for interaction, functional knockdown with partial pathway rescue, single lab, no in vitro reconstitution","pmids":["39118123"],"is_preprint":false},{"year":2025,"finding":"PCIF1-mediated m6Am methylation at the MTF2 mRNA 5' cap selectively suppresses MTF2 translation; PCIF1 knockdown reduces OSCC progression, while MTF2 knockdown counteracts this protective effect, placing MTF2 downstream of PCIF1 in a post-transcriptional regulatory axis.","method":"m6Am methylation mapping, PCIF1 knockdown and MTF2 knockdown in OSCC cell lines and in vivo mouse models, Western blot for MTF2 protein, polysome profiling (implied), rescue assays","journal":"Clinical and translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — m6Am modification identified with functional validation by epistasis (KD rescue), in vivo model, single lab","pmids":["40156159"],"is_preprint":false},{"year":2025,"finding":"MTF2 stimulates PRC2.1-mediated repression in human pluripotent stem cells and cardiac differentiation through its interactions with both DNA and H3K36me3; MTF2-PRC2.1 maintains normal cardiomyocyte function and action potential rhythm; PHF19 antagonizes MTF2 function in this context.","method":"Separation-of-function mutants in human PSCs, ChIP-seq for H3K27me3, cardiomyocyte differentiation assays, electrophysiology for action potential measurement","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — separation-of-function mutants with ChIP-seq and functional differentiation assays, preprint, single lab","pmids":[],"is_preprint":true},{"year":2025,"finding":"De novo DNA methylation at bivalent promoters leads to reduced MTF2 binding and eviction of H3K27me3, resulting in gene activation; this demonstrates that MTF2 binding to unmethylated CpG-rich regions is required for maintaining H3K27me3 at bivalent loci.","method":"Hit-and-run CRISPR/dCas9 epigenome editing to deposit DNA methylation, ChIP-seq for MTF2 and H3K27me3, comparison of methylated vs. unmethylated promoters","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct epigenome editing with ChIP-seq readout, functional consequence demonstrated, preprint, single lab","pmids":[],"is_preprint":true},{"year":2024,"finding":"EPOP disrupts the PRC2.1 dimer and reduces chromatin association; an EPOP mutant defective in PRC2 binding enhances genome-wide enrichment of MTF2 and H3K27me3, indicating that MTF2-PRC2.1 dimerization contributes to its avidity-dependent chromatin binding.","method":"EPOP PRC2-binding mutant in mouse epiblast-like cells, ChIP-seq for MTF2 and H3K27me3, biochemical analysis of PRC2.1 oligomerization state","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — indirect evidence for MTF2 from EPOP mutant experiments, preprint, single lab","pmids":[],"is_preprint":true}],"current_model":"MTF2 (PCL2) is an accessory subunit of the PRC2.1 complex that directly binds unmethylated CpG-rich DNA regions with reduced helix twist, thereby recruiting PRC2 to target loci and stimulating its histone methyltransferase activity to deposit H3K27me3; it also interacts directly with EZH2, modulates PRC2 catalytic activity in a context-dependent manner (activating or suppressing it at specific loci such as Hox genes vs. Cdkn2a), represses MDM2 to maintain p53 stability, and is essential for definitive erythropoiesis by globally maintaining H3K27me3 and repressing Wnt signaling."},"narrative":{"mechanistic_narrative":"MTF2 (PCL2) is an accessory subunit of the Polycomb Repressive Complex 2 (PRC2.1) that targets the complex to chromatin and tunes its catalytic output to control developmental gene repression [PMID:29808031, PMID:21059868]. It directly binds DNA in a methylation-sensitive manner, selectively recognizing high-density unmethylated CpG regions in a context of reduced helix twist, and this recognition is required for genome-wide recruitment of the catalytic subunit EZH2 and deposition of H3K27me3 [PMID:29808031]; de novo DNA methylation evicts MTF2 and the H3K27me3 mark, confirming that unmethylated CpG binding is necessary to maintain repression at bivalent promoters. Within reconstituted PRC2, MTF2 acts together with JARID2 and esPRC2p48/EPOP to stimulate histone methyltransferase activity and to nucleate H3K27me3 at chromatin in a DNA-sequence-dependent (GCN/GCN-rich) manner [PMID:21732481, PMID:41650228]. MTF2 interacts directly with EZH2 through its PHD finger and functions as a transcriptional repressor, but its effect on PRC2 catalysis is context-dependent, repressing Hox loci while locally suppressing PRC2 activity to permit Cdkn2a expression [PMID:21059868, PMID:15294861]. Through these activities MTF2 enforces silencing of pluripotency factors and developmental regulators, and is essential for definitive erythropoiesis, where its loss causes global H3K27me3 depletion, de-repression of canonical Wnt signaling, and lethal anemia [PMID:29736258, PMID:21193838]. Beyond its PRC2 role, MTF2-PRC2 directly represses MDM2 to sustain p53 stability and chemosensitivity in hematopoietic cells [PMID:30115703].","teleology":[{"year":2004,"claim":"Established the first molecular function for the MTF2 ortholog by showing it is a PHD-finger transcriptional repressor that physically engages the PRC2 catalytic subunit EZH2 and silences a developmental gene in vivo.","evidence":"In vitro PHD-EZH2 pulldown, repression-domain mapping, Shh promoter luciferase, and gain/loss-of-function in chick embryos","pmids":["15294861"],"confidence":"High","gaps":["Did not define DNA-binding specificity or genome-wide targets","Mechanism of how EZH2 binding modulates catalysis unresolved"]},{"year":2010,"claim":"Showed that MTF2/Pcl2 is a PRC2-associated factor required for Hox repression but with locus-dependent, even opposing, effects on PRC2 catalytic output.","evidence":"Reciprocal Co-IP, ChIP, and conditional knockout/knockdown mouse genetics with expression analysis","pmids":["21059868"],"confidence":"High","gaps":["Did not explain mechanistically why Pcl2 activates versus represses different loci","No direct DNA-binding readout"]},{"year":2011,"claim":"Defined MTF2 as a functional PRC2 subunit that, with JARID2 and esPRC2p48, stimulates histone methyltransferase activity and controls ESC differentiation gene programs.","evidence":"Co-IP, in vitro HMT assay with reconstituted PRC2, siRNA knockdown in ES cells (two independent studies)","pmids":["21732481","21193838"],"confidence":"High","gaps":["Did not identify what directs MTF2/PRC2 to specific loci","Stimulation mechanism on the enzyme not structurally resolved"]},{"year":2018,"claim":"Resolved the recruitment mechanism by showing MTF2 directly reads unmethylated CpG-dense DNA with reduced helix twist and that this is essential for genome-wide EZH2 recruitment and H3K27me3.","evidence":"MTF2 knockout ESCs, EZH2/H3K27me3 ChIP-seq, in vitro DNA binding, and genome-wide CpG/helix-twist analysis","pmids":["29808031"],"confidence":"High","gaps":["Structural basis of helix-twist recognition not determined","How DNA reading is coupled to enzyme stimulation unresolved"]},{"year":2018,"claim":"Demonstrated an in vivo physiological requirement for MTF2 in definitive erythropoiesis, linking its loss to global H3K27me3 collapse and Wnt de-repression.","evidence":"Conditional Mtf2 knockout mice, H3K27me3 ChIP-seq, PRC2 protein blots, and chemical Wnt-inhibitor rescue in vitro","pmids":["29736258"],"confidence":"High","gaps":["Direct targets bridging H3K27me3 loss to Wnt activation not fully enumerated","Whether Wnt is the sole effector pathway unresolved"]},{"year":2018,"claim":"Extended MTF2 function beyond chromatin by showing MTF2-PRC2 directly represses MDM2 to preserve p53, with therapeutic relevance in AML.","evidence":"MTF2 perturbation in CD34+CD38- AML cells, ChIP-seq, patient-derived xenograft model, and MDM2-inhibitor rescue","pmids":["30115703"],"confidence":"Medium","gaps":["Single lab; reciprocal validation of the MDM2 repression axis limited","Relationship between PRC2-dependent and p53-axis roles not integrated"]},{"year":2023,"claim":"Proposed a parallel, non-transcriptional route to p53 stabilization in which PCL2 sequesters MDM2 in the nucleolus to block p53 ubiquitination.","evidence":"PCL2 overexpression/knockdown in breast cancer cells, Co-IP, ubiquitination assay, and MDM2 nucleolar localization imaging","pmids":["36658883"],"confidence":"Medium","gaps":["Single lab; how nucleolar sequestration relates to chromatin role unclear","Direct MTF2-MDM2 binding interface not mapped"]},{"year":2024,"claim":"Reported a cancer-promoting MTF2-EZH2 axis in osteosarcoma acting through SFRP1 silencing and Wnt activation.","evidence":"Single Co-IP for MTF2-EZH2, siRNA knockdown, and SFRP1/EZH2 rescue experiments","pmids":["39118123"],"confidence":"Low","gaps":["Single Co-IP without reciprocal or reconstituted validation","Direct vs. indirect silencing of SFRP1 not distinguished"]},{"year":2025,"claim":"Refined the biochemical model showing MTF2 stimulates PRC2 HMT activity and nucleates H3K27me3 at chromatin in a DNA-sequence-dependent manner with JARID2 and EPOP, and reads H3K36me3 to direct PRC2.1 in human stem/cardiac contexts.","evidence":"In vitro HMT and dinucleosome binding assays with reconstituted PRC2, EED-rescue in vivo; separation-of-function mutants in human PSCs with ChIP-seq and electrophysiology (preprint)","pmids":["41650228"],"confidence":"High","gaps":["Structural coupling of DNA/H3K36me3 reading to catalysis not solved","Cardiac PSC findings are preprint and single lab"]},{"year":2025,"claim":"Showed MTF2 is itself regulated, both upstream (PCIF1-mediated m6Am suppresses MTF2 translation) and through chromatin context (de novo DNA methylation evicts MTF2 and H3K27me3).","evidence":"m6Am mapping with PCIF1/MTF2 knockdown epistasis in OSCC; dCas9 epigenome editing with MTF2/H3K27me3 ChIP-seq (preprint)","pmids":["40156159"],"confidence":"Medium","gaps":["Polysome-level translational control inferred, not fully resolved","Epigenome-editing eviction result is preprint and single lab"]},{"year":null,"claim":"How MTF2 mechanistically switches between activating and suppressing PRC2 catalysis at different loci, and the structural basis of its combined CpG-DNA and H3K36me3 reading, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of MTF2 bound to its DNA/nucleosome targets","Determinants of context-dependent activation vs. repression undefined","Integration of chromatin and MDM2/p53 roles unestablished"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0,7,12]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[2,3]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1,7]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[11]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,2]},{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[8]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,2,5]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[3,6]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[5,11]}],"complexes":["PRC2.1"],"partners":["EZH2","JARID2","EPOP","EED","MDM2","PHF19"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y483","full_name":"Metal-response element-binding transcription factor 2","aliases":["Metal regulatory transcription factor 2","Metal-response element DNA-binding protein M96","Polycomb-like protein 2","hPCl2"],"length_aa":593,"mass_kda":67.1,"function":"Polycomb group (PcG) protein that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex, thus enhancing PRC2 H3K27me3 methylation activity (PubMed:23142980, PubMed:23228662, PubMed:31959557). Regulates the transcriptional networks during embryonic stem cell self-renewal and differentiation (By similarity). Promotes recruitment of the PRC2 complex to the inactive X chromosome in differentiating XX ES cells and PRC2 recruitment to target genes in undifferentiated ES cells (By similarity). Required to repress Hox genes by enhancing H3K27me3 methylation of the PRC2 complex (By similarity). In some conditions may act as an inhibitor of PRC2 activity: able to activate the CDKN2A gene and promote cellular senescence by suppressing the catalytic activity of the PRC2 complex locally (By similarity). Binds to the metal-regulating-element (MRE) of MT1A gene promoter (By similarity)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9Y483/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MTF2","classification":"Not Classified","n_dependent_lines":25,"n_total_lines":1208,"dependency_fraction":0.020695364238410598},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"NUCKS1","stoichiometry":4.0},{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"HMGA1","stoichiometry":0.2},{"gene":"HMGN5","stoichiometry":0.2},{"gene":"NUMA1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/MTF2","total_profiled":1310},"omim":[{"mim_id":"618365","title":"ZINC FINGER- AND SCAN DOMAIN-CONTAINING PROTEIN 10; ZSCAN10","url":"https://www.omim.org/entry/618365"},{"mim_id":"617795","title":"ELONGIN BC- AND POLYCOMB REPRESSIVE COMPLEX 2-ASSOCIATED PROTEIN; EPOP","url":"https://www.omim.org/entry/617795"},{"mim_id":"609882","title":"METAL-REGULATORY TRANSCRIPTION FACTOR 2; MTF2","url":"https://www.omim.org/entry/609882"},{"mim_id":"609740","title":"PHD FINGER PROTEIN 19; PHF19","url":"https://www.omim.org/entry/609740"},{"mim_id":"607698","title":"LIGAND-DEPENDENT NUCLEAR RECEPTOR COREPRESSOR; LCOR","url":"https://www.omim.org/entry/607698"}],"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/MTF2"},"hgnc":{"alias_symbol":["M96","PCL2","TDRD19A"],"prev_symbol":[]},"alphafold":{"accession":"Q9Y483","domains":[{"cath_id":"2.30.30.140","chopping":"49-94","consensus_level":"high","plddt":95.3217,"start":49,"end":94},{"cath_id":"3.30.40.10","chopping":"99-149","consensus_level":"medium","plddt":90.6508,"start":99,"end":149},{"cath_id":"1.10.10","chopping":"265-345","consensus_level":"medium","plddt":96.6573,"start":265,"end":345}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y483","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y483-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y483-F1-predicted_aligned_error_v6.png","plddt_mean":70.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MTF2","jax_strain_url":"https://www.jax.org/strain/search?query=MTF2"},"sequence":{"accession":"Q9Y483","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y483.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y483/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y483"}},"corpus_meta":[{"pmid":"7973731","id":"PMC_7973731","title":"The PCL2 (ORFD)-PHO85 cyclin-dependent kinase complex: a cell cycle regulator in yeast.","date":"1994","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/7973731","citation_count":153,"is_preprint":false},{"pmid":"29808031","id":"PMC_29808031","title":"MTF2 recruits Polycomb Repressive Complex 2 by helical-shape-selective DNA binding.","date":"2018","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/29808031","citation_count":144,"is_preprint":false},{"pmid":"21732481","id":"PMC_21732481","title":"PRC2 complexes with JARID2, MTF2, and esPRC2p48 in ES cells to modulate ES cell pluripotency and somatic cell reprogramming.","date":"2011","source":"Stem cells (Dayton, Ohio)","url":"https://pubmed.ncbi.nlm.nih.gov/21732481","citation_count":127,"is_preprint":false},{"pmid":"21059868","id":"PMC_21059868","title":"Mammalian polycomb-like Pcl2/Mtf2 is a novel regulatory component of PRC2 that can differentially modulate polycomb activity both at the Hox gene 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& general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/8413192","citation_count":38,"is_preprint":false},{"pmid":"15294861","id":"PMC_15294861","title":"Chick Pcl2 regulates the left-right asymmetry by repressing Shh expression in Hensen's node.","date":"2004","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/15294861","citation_count":32,"is_preprint":false},{"pmid":"21193838","id":"PMC_21193838","title":"PCL2 modulates gene regulatory networks controlling self-renewal and commitment in embryonic stem cells.","date":"2011","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/21193838","citation_count":31,"is_preprint":false},{"pmid":"34265414","id":"PMC_34265414","title":"LncRNA CCAT1 sponges miR-218-5p to promote EMT, cellular migration and invasion of retinoblastoma by targeting MTF2.","date":"2021","source":"Cellular 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medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40156159","citation_count":1,"is_preprint":false},{"pmid":"38499152","id":"PMC_38499152","title":"Sls1 and Mtf2 mediate the assembly of the Mrh5C complex required for activation of cox1 mRNA translation.","date":"2024","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/38499152","citation_count":1,"is_preprint":false},{"pmid":"39118123","id":"PMC_39118123","title":"MTF2 facilitates the advancement of osteosarcoma through mediating EZH2/SFRP1/Wnt signaling.","date":"2024","source":"Journal of orthopaedic surgery and research","url":"https://pubmed.ncbi.nlm.nih.gov/39118123","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.09.687442","title":"Distinct regulation of AEBP2 isoforms on PRC2 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methylation-sensitive manner, selectively recognizing regions with high density of unmethylated CpGs in a context of reduced helix twist, and is essential for genome-wide recruitment of the PRC2 catalytic subunit EZH2 to target genes in mouse embryonic stem cells; MTF2 knockout abolishes EZH2 recruitment and greatly reduces H3K27me3 deposition.\",\n      \"method\": \"MTF2 knockout ESCs, ChIP-seq for EZH2 and H3K27me3, in vitro DNA binding assays, genome-wide analysis of CpG methylation and helix twist\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (KO, ChIP-seq, in vitro binding), replicated in both in vitro and in vivo contexts in a single rigorous study\",\n      \"pmids\": [\"29808031\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"MTF2 is a component of the PRC2 complex in mouse ES cells and, together with JARID2 and esPRC2p48, synergistically stimulates the histone methyltransferase activity of PRC2 in vitro; knockdown of MTF2 alters H3K27 methylation levels and causes expression of differentiation-associated genes.\",\n      \"method\": \"Co-immunoprecipitation, in vitro histone methyltransferase assay with reconstituted PRC2 complex, siRNA knockdown in ES cells, gene expression analysis\",\n      \"journal\": \"Stem cells (Dayton, Ohio)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro enzymatic reconstitution assay combined with Co-IP and functional KD, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"21732481\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Pcl2/Mtf2 forms a complex with PRC2 and binds to Hox gene loci in a PRC2-dependent manner; it is required for PRC2-mediated Hox gene repression and exhibits a synergistic effect on PRC1-mediated Hox repression without major alterations in H3K27me3 or PRC1 deposition; paradoxically, in embryonic fibroblasts Pcl2 activates Cdkn2a expression by locally suppressing PRC2 catalytic activity.\",\n      \"method\": \"Co-immunoprecipitation, ChIP, conditional knockout and knockdown mouse genetics, gene expression analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, ChIP, in vivo genetic models, multiple orthogonal methods\",\n      \"pmids\": [\"21059868\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Chick Pcl2 (ortholog of MTF2) functions as a transcriptional repressor through its PHD finger domain; it directly interacts with EZH2 (a PRC2 component) via pulldown assay, represses Shh promoter activity in vitro, and regulates left-right axis patterning in chick embryos by silencing Shh expression in the right side of Hensen's node.\",\n      \"method\": \"In vitro pulldown assay (PHD finger–EZH2 interaction), in vitro transcription repression mapping, gain- and loss-of-function in chick embryos, luciferase reporter assay for Shh promoter\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — direct binding demonstrated by pulldown, functional domain mapping, in vivo rescue, multiple orthogonal assays in single study\",\n      \"pmids\": [\"15294861\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MTF2-PRC2 directly represses MDM2 in hematopoietic cells; loss of MTF2 results in overexpression of MDM2, which inhibits p53, leading to defects in cell-cycle regulation and apoptosis and chemoresistance in AML; overexpression of MTF2 or MDM2 inhibitors restored p53 activity and chemosensitivity.\",\n      \"method\": \"MTF2 overexpression/knockdown in CD34+CD38- AML cells, ChIP-seq, patient-derived xenograft mouse model, MDM2 inhibitor treatment, gene expression and apoptosis assays\",\n      \"journal\": \"Cancer discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP-seq evidence of direct repression, in vivo PDX model, functional rescue, single lab\",\n      \"pmids\": [\"30115703\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Mtf2 is required for maintenance of core PRC2 protein levels and global H3K27me3 at promoter-proximal regions in erythroid progenitors; Mtf2-knockout embryos show global loss of H3K27me3, de-repression of canonical Wnt signaling, and die by e15.5 due to severe anemia; chemical inhibition of Wnt signaling rescued Mtf2-deficient erythroblast differentiation in vitro.\",\n      \"method\": \"Conditional Mtf2 knockout mice, ChIP-seq for H3K27me3, Western blot for PRC2 core proteins, gene regulatory network analysis, chemical Wnt inhibitor rescue in vitro\",\n      \"journal\": \"Cell discovery\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo KO with defined phenotype, ChIP-seq, protein level analysis, pathway-specific rescue, multiple orthogonal methods\",\n      \"pmids\": [\"29736258\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"PCL2 depletion in ESCs leads to decreased H3K27me3 at promoters of pluripotency transcription factors Tbx3, Klf4, and Foxd3, with concomitant upregulation of these genes, which subsequently activate Oct4, Nanog, and Sox2 through a feed-forward circuit, increasing self-renewal and delaying differentiation.\",\n      \"method\": \"siRNA knockdown in mouse ESCs, ChIP for H3K27me3 at specific promoters, gene expression analysis, flow cytometry for pluripotency markers\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP at specific loci combined with gene expression changes and functional phenotype, single lab\",\n      \"pmids\": [\"21193838\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MTF2 stimulates PRC2 histone methyltransferase (HMT) activity in vitro using reconstituted substrates; MTF2 promotes PRC2 chromatin-binding activity in a DNA-sequence-dependent manner (GCN-rich sequences); MTF2 together with JARID2 and EPOP fosters PRC2-mediated H3K27me3 deposition at chromatin nucleation sites.\",\n      \"method\": \"In vitro HMT assay with reconstituted PRC2, binding assays with reconstituted dinucleosome substrates, EED-rescue system in vivo for chromatin recruitment\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution assay with defined substrates and in vivo EED-rescue system, multiple orthogonal approaches in single study\",\n      \"pmids\": [\"41650228\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PCL2 protects p53 from MDM2-mediated ubiquitination and degradation by sequestering MDM2 into the nucleolus, thereby elevating p53 protein stability and increasing expression of p53 target genes in breast cancer cells.\",\n      \"method\": \"PCL2 overexpression and knockdown in breast cancer cells, co-immunoprecipitation, ubiquitination assay, Western blot, subcellular fractionation/immunofluorescence for MDM2 nucleolar localization\",\n      \"journal\": \"Science bulletin\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, ubiquitination assay, subcellular localization experiment with functional consequence, single lab\",\n      \"pmids\": [\"36658883\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"MTF2 directly binds to EZH2 in osteosarcoma cells and promotes EZH2-mediated silencing of SFRP1, thereby activating Wnt signaling to drive osteosarcoma progression; EZH2 upregulation or SFRP1 antagonism counteracted effects of MTF2 knockdown.\",\n      \"method\": \"Co-immunoprecipitation (Co-IP) assay for MTF2-EZH2 interaction, siRNA knockdown, Western blot, cell proliferation/invasion/apoptosis assays, rescue experiments\",\n      \"journal\": \"Journal of orthopaedic surgery and research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP for interaction, functional knockdown with partial pathway rescue, single lab, no in vitro reconstitution\",\n      \"pmids\": [\"39118123\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PCIF1-mediated m6Am methylation at the MTF2 mRNA 5' cap selectively suppresses MTF2 translation; PCIF1 knockdown reduces OSCC progression, while MTF2 knockdown counteracts this protective effect, placing MTF2 downstream of PCIF1 in a post-transcriptional regulatory axis.\",\n      \"method\": \"m6Am methylation mapping, PCIF1 knockdown and MTF2 knockdown in OSCC cell lines and in vivo mouse models, Western blot for MTF2 protein, polysome profiling (implied), rescue assays\",\n      \"journal\": \"Clinical and translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — m6Am modification identified with functional validation by epistasis (KD rescue), in vivo model, single lab\",\n      \"pmids\": [\"40156159\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MTF2 stimulates PRC2.1-mediated repression in human pluripotent stem cells and cardiac differentiation through its interactions with both DNA and H3K36me3; MTF2-PRC2.1 maintains normal cardiomyocyte function and action potential rhythm; PHF19 antagonizes MTF2 function in this context.\",\n      \"method\": \"Separation-of-function mutants in human PSCs, ChIP-seq for H3K27me3, cardiomyocyte differentiation assays, electrophysiology for action potential measurement\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — separation-of-function mutants with ChIP-seq and functional differentiation assays, preprint, single lab\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"De novo DNA methylation at bivalent promoters leads to reduced MTF2 binding and eviction of H3K27me3, resulting in gene activation; this demonstrates that MTF2 binding to unmethylated CpG-rich regions is required for maintaining H3K27me3 at bivalent loci.\",\n      \"method\": \"Hit-and-run CRISPR/dCas9 epigenome editing to deposit DNA methylation, ChIP-seq for MTF2 and H3K27me3, comparison of methylated vs. unmethylated promoters\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct epigenome editing with ChIP-seq readout, functional consequence demonstrated, preprint, single lab\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"EPOP disrupts the PRC2.1 dimer and reduces chromatin association; an EPOP mutant defective in PRC2 binding enhances genome-wide enrichment of MTF2 and H3K27me3, indicating that MTF2-PRC2.1 dimerization contributes to its avidity-dependent chromatin binding.\",\n      \"method\": \"EPOP PRC2-binding mutant in mouse epiblast-like cells, ChIP-seq for MTF2 and H3K27me3, biochemical analysis of PRC2.1 oligomerization state\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — indirect evidence for MTF2 from EPOP mutant experiments, preprint, single lab\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"MTF2 (PCL2) is an accessory subunit of the PRC2.1 complex that directly binds unmethylated CpG-rich DNA regions with reduced helix twist, thereby recruiting PRC2 to target loci and stimulating its histone methyltransferase activity to deposit H3K27me3; it also interacts directly with EZH2, modulates PRC2 catalytic activity in a context-dependent manner (activating or suppressing it at specific loci such as Hox genes vs. Cdkn2a), represses MDM2 to maintain p53 stability, and is essential for definitive erythropoiesis by globally maintaining H3K27me3 and repressing Wnt signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MTF2 (PCL2) is an accessory subunit of the Polycomb Repressive Complex 2 (PRC2.1) that targets the complex to chromatin and tunes its catalytic output to control developmental gene repression [#0, #2]. It directly binds DNA in a methylation-sensitive manner, selectively recognizing high-density unmethylated CpG regions in a context of reduced helix twist, and this recognition is required for genome-wide recruitment of the catalytic subunit EZH2 and deposition of H3K27me3 [#0]; de novo DNA methylation evicts MTF2 and the H3K27me3 mark, confirming that unmethylated CpG binding is necessary to maintain repression at bivalent promoters [#12]. Within reconstituted PRC2, MTF2 acts together with JARID2 and esPRC2p48/EPOP to stimulate histone methyltransferase activity and to nucleate H3K27me3 at chromatin in a DNA-sequence-dependent (GCN/GCN-rich) manner [#1, #7]. MTF2 interacts directly with EZH2 through its PHD finger and functions as a transcriptional repressor, but its effect on PRC2 catalysis is context-dependent, repressing Hox loci while locally suppressing PRC2 activity to permit Cdkn2a expression [#2, #3]. Through these activities MTF2 enforces silencing of pluripotency factors and developmental regulators, and is essential for definitive erythropoiesis, where its loss causes global H3K27me3 depletion, de-repression of canonical Wnt signaling, and lethal anemia [#5, #6]. Beyond its PRC2 role, MTF2-PRC2 directly represses MDM2 to sustain p53 stability and chemosensitivity in hematopoietic cells [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Established the first molecular function for the MTF2 ortholog by showing it is a PHD-finger transcriptional repressor that physically engages the PRC2 catalytic subunit EZH2 and silences a developmental gene in vivo.\",\n      \"evidence\": \"In vitro PHD-EZH2 pulldown, repression-domain mapping, Shh promoter luciferase, and gain/loss-of-function in chick embryos\",\n      \"pmids\": [\"15294861\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define DNA-binding specificity or genome-wide targets\", \"Mechanism of how EZH2 binding modulates catalysis unresolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Showed that MTF2/Pcl2 is a PRC2-associated factor required for Hox repression but with locus-dependent, even opposing, effects on PRC2 catalytic output.\",\n      \"evidence\": \"Reciprocal Co-IP, ChIP, and conditional knockout/knockdown mouse genetics with expression analysis\",\n      \"pmids\": [\"21059868\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not explain mechanistically why Pcl2 activates versus represses different loci\", \"No direct DNA-binding readout\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined MTF2 as a functional PRC2 subunit that, with JARID2 and esPRC2p48, stimulates histone methyltransferase activity and controls ESC differentiation gene programs.\",\n      \"evidence\": \"Co-IP, in vitro HMT assay with reconstituted PRC2, siRNA knockdown in ES cells (two independent studies)\",\n      \"pmids\": [\"21732481\", \"21193838\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify what directs MTF2/PRC2 to specific loci\", \"Stimulation mechanism on the enzyme not structurally resolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Resolved the recruitment mechanism by showing MTF2 directly reads unmethylated CpG-dense DNA with reduced helix twist and that this is essential for genome-wide EZH2 recruitment and H3K27me3.\",\n      \"evidence\": \"MTF2 knockout ESCs, EZH2/H3K27me3 ChIP-seq, in vitro DNA binding, and genome-wide CpG/helix-twist analysis\",\n      \"pmids\": [\"29808031\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of helix-twist recognition not determined\", \"How DNA reading is coupled to enzyme stimulation unresolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Demonstrated an in vivo physiological requirement for MTF2 in definitive erythropoiesis, linking its loss to global H3K27me3 collapse and Wnt de-repression.\",\n      \"evidence\": \"Conditional Mtf2 knockout mice, H3K27me3 ChIP-seq, PRC2 protein blots, and chemical Wnt-inhibitor rescue in vitro\",\n      \"pmids\": [\"29736258\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct targets bridging H3K27me3 loss to Wnt activation not fully enumerated\", \"Whether Wnt is the sole effector pathway unresolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extended MTF2 function beyond chromatin by showing MTF2-PRC2 directly represses MDM2 to preserve p53, with therapeutic relevance in AML.\",\n      \"evidence\": \"MTF2 perturbation in CD34+CD38- AML cells, ChIP-seq, patient-derived xenograft model, and MDM2-inhibitor rescue\",\n      \"pmids\": [\"30115703\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab; reciprocal validation of the MDM2 repression axis limited\", \"Relationship between PRC2-dependent and p53-axis roles not integrated\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Proposed a parallel, non-transcriptional route to p53 stabilization in which PCL2 sequesters MDM2 in the nucleolus to block p53 ubiquitination.\",\n      \"evidence\": \"PCL2 overexpression/knockdown in breast cancer cells, Co-IP, ubiquitination assay, and MDM2 nucleolar localization imaging\",\n      \"pmids\": [\"36658883\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab; how nucleolar sequestration relates to chromatin role unclear\", \"Direct MTF2-MDM2 binding interface not mapped\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Reported a cancer-promoting MTF2-EZH2 axis in osteosarcoma acting through SFRP1 silencing and Wnt activation.\",\n      \"evidence\": \"Single Co-IP for MTF2-EZH2, siRNA knockdown, and SFRP1/EZH2 rescue experiments\",\n      \"pmids\": [\"39118123\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP without reciprocal or reconstituted validation\", \"Direct vs. indirect silencing of SFRP1 not distinguished\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Refined the biochemical model showing MTF2 stimulates PRC2 HMT activity and nucleates H3K27me3 at chromatin in a DNA-sequence-dependent manner with JARID2 and EPOP, and reads H3K36me3 to direct PRC2.1 in human stem/cardiac contexts.\",\n      \"evidence\": \"In vitro HMT and dinucleosome binding assays with reconstituted PRC2, EED-rescue in vivo; separation-of-function mutants in human PSCs with ChIP-seq and electrophysiology (preprint)\",\n      \"pmids\": [\"41650228\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural coupling of DNA/H3K36me3 reading to catalysis not solved\", \"Cardiac PSC findings are preprint and single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed MTF2 is itself regulated, both upstream (PCIF1-mediated m6Am suppresses MTF2 translation) and through chromatin context (de novo DNA methylation evicts MTF2 and H3K27me3).\",\n      \"evidence\": \"m6Am mapping with PCIF1/MTF2 knockdown epistasis in OSCC; dCas9 epigenome editing with MTF2/H3K27me3 ChIP-seq (preprint)\",\n      \"pmids\": [\"40156159\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Polysome-level translational control inferred, not fully resolved\", \"Epigenome-editing eviction result is preprint and single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How MTF2 mechanistically switches between activating and suppressing PRC2 catalysis at different loci, and the structural basis of its combined CpG-DNA and H3K36me3 reading, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of MTF2 bound to its DNA/nucleosome targets\", \"Determinants of context-dependent activation vs. repression undefined\", \"Integration of chromatin and MDM2/p53 roles unestablished\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0, 7, 12]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1, 7]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 2, 5]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [3, 6]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [5, 11]}\n    ],\n    \"complexes\": [\"PRC2.1\"],\n    \"partners\": [\"EZH2\", \"JARID2\", \"EPOP\", \"EED\", \"MDM2\", \"PHF19\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}