EZH2 is the catalytic lysine methyltransferase of Polycomb repressive complex 2 (PRC2). Its SET domain transfers methyl groups from S-adenosylmethionine to histone H3 lysine 27, producing mono-, di- and trimethylated states in a reaction supported by EED, SUZ12 and other complex components. On chromatin, EZH2 contacts nucleosomal DNA and the H3 tail, while partner proteins supply additional recognition and targeting functions. EED recognizes methylated ligands and allosterically stimulates the EZH2 catalytic site. This system contributes to facultative heterochromatin and repression of transcription, helping maintain regulated gene-expression programs. EZH2-containing complexes also methylate substrates including histone H1.4 and JARID2 in defined biochemical settings. EZH2 binds long noncoding RNAs, providing a further interface between PRC2 and regulatory transcripts; the consequences depend on the RNA and complex context. Germline EZH2 variants cause Weaver syndrome, an overgrowth disorder; several tested syndrome-associated variants reduce PRC2 methyltransferase activity. Somatic lymphoma-associated SET-domain variants alter methylation-state preference and can increase H3K27 trimethylation through different biochemical mechanisms.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | ACCEPT | Summary: EZH2 represses transcription from a chromatin-bound target promoter. Reason: In PMID:20154697, ectopic EZH2 reduces DAB2IP mRNA and protein in human prostate epithelial cells and ChIP detects EZH2 at the DAB2IP promoter. This is direct promoter-associated repression; the downstream signaling phenotypes are considered separately. Correction PMID:38383797 replaces a Ki-67 control micrograph in Figure1g and does not retract the EZH2 experiments in Figure5. Supporting Evidence: |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: EZH2 contributes to repression of RNA polymerase II transcription. Reason: The rat donor currently carries PMID23932971 IMP; its operative full text was not recovered. Independent actual human EZH2 reporter and rescue experiments in PMID16717091 support repression in the CLOCK–BMAL1/CRY context, while PRC2 chromatin methylation supplies a broader mechanistic basis. Human EZH2 constructs, mouse promoters and the HeLa or NIH3T3 hosts remain distinct; this acceptance does not claim the rat neuronal experiment was read. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | NAS PMID:29348366 Structures of human PRC2 with its cofactors AEBP2 and JARID2... | ACCEPT | Summary: Repression of RNA polymerase II transcription is a core PRC2-associated role. Reason: PMID:29348366 describes human PRC2 structures and the repressive H3K27 methylation system. This NAS statement is consistent with direct human repression experiments inspected in PMID:20154697 and PMID:26581166; it is not treated as a new transcription assay performed by the structural study. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | NAS PMID:35800061 PRC2, Chromatin Regulation, and Human Disease: Insights From... | ACCEPT | Summary: EZH2-associated PRC2 represses RNA polymerase II transcription. Reason: PMID:35800061 is a review summarizing H3K27 methylation and Polycomb repression, appropriately a NAS source. The biological role is independently established by the human primary studies inspected here; the review is not represented as original experimental evidence. |
| GO:0000781 chromosome, telomeric region | IGI PMID:9214638 Mammalian homologues of the Polycomb-group gene Enhancer of ... | UNDECIDED | Summary: Native human telomeric localization is not resolved by the accessible evidence. Reason: The PMID:9214638 abstract explicitly tests human EZH2 in transgenic fly and yeast silencing assays. Functional complementation at a yeast telomere does not alone demonstrate native human telomeric localization. The original full text could not be recovered through the attempted routes, so retain the original IGI source object and leave this specific location undecided rather than alleging a curator error. |
| GO:0000785 chromatin | IDA PMID:19734898 The histone variant macroH2A is an epigenetic regulator of k... | ACCEPT | Summary: EZH2 acts on and associates with chromatin. Reason: PMID:19734898 describes overlap of macroH2A and PRC2 at genes in human male pluripotent cells, but its complete EZH2-specific assays were inaccessible. Retain this clearly established broad location on independent human ChIP and nucleosome-structure evidence in PMID:20154697 and PMID:33479123, without pretending to have inspected the missing original panels. |
| GO:0000792 heterochromatin | IDA PMID:15231737 Silencing of human polycomb target genes is associated with ... | ACCEPT | Summary: EZH2 occupies transcriptionally repressed chromatin. Reason: PMID:15231737 reports human SW480 EZH2 ChIP at MYT1 and other repressed promoters with H3K27me3. Retain the broad heterochromatin location in this facultative repressive context. The tested pericentromeric HTF6 promoter lacked EZH2 enrichment, so the annotation is not expanded to constitutive or pericentromeric heterochromatin. Supporting Evidence: |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000107 | ACCEPT | Summary: EZH2 associates with transcriptional cis-regulatory chromatin. Reason: The rat PMID22821416 donor experiment remains unread beyond available summary material. GO:0000976 explicitly includes non-sequence-specific binding within regulatory DNA. Independently, human ES-cell EZH2 ChIP at regulatory loci in PMID20064375 and direct EZH2 contacts with nucleosomal DNA in human PRC2 in PMID33479123 support this broad assertion. These results do not establish an intrinsic EZH2 promoter-recognition sequence. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Retain chromatin DNA binding without assigning intrinsic sequence recognition. Reason: The exact mouse donor is PMID24137001 IDA. Its Ezh2 ChIP/RNA-ChIP supports locus association, but the inspected RNA–DNA hybrid assay contains synthetic nucleic acids rather than EZH2 protein. Human PRC2 structures independently show EZH2 SET/CXC/bridge-helix contacts with nucleosomal DNA. Chromatin DNA binding captures the positive evidence without making an unsupported sequence-discrimination claim. Proposed replacements: chromatin DNA binding |
| GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Refine promoter occupancy to demonstrated chromatin DNA binding. Reason: Current mouse donor records cite PMID16717091 IMP and PMID20798045 IDA. The first measures promoter occupancy and repression; the inspected Figure 2D of the latter is H3K27me3 ChIP. Neither inspected experiment establishes EZH2 recognition of a core-promoter sequence. Direct human PRC2 DNA contacts support GO:0031490 independently, preserving the positive chromatin association. Proposed replacements: chromatin DNA binding |
| GO:0001222 transcription corepressor binding | IPI PMID:29628311 A Family of Vertebrate-Specific Polycombs Encoded by the LCO... | UNDECIDED | Summary: The precise PALI2/LCORL corepressor-binding context remains unverified. Reason: The PMID:29628311 abstract identifies PALI1/PALI2-containing PRC2.1, but the original interaction data and repository PDF were inaccessible. The supplied Q8N3X6 partner and assay cannot be resolved from a general complex summary alone. Preserve this experimental annotation as undecided rather than substituting a guessed partner mechanism. |
| GO:0001222 transcription corepressor binding | IPI PMID:29628311 A Family of Vertebrate-Specific Polycombs Encoded by the LCO... | UNDECIDED | Summary: The precise PALI1/LCOR corepressor-binding context remains unverified. Reason: The PMID:29628311 abstract establishes PALI1/2 as PRC2.1-associated proteins, but the complete interaction experiments were inaccessible. The supplied Q96JN0 protein identity does not by itself establish which LCOR product or direct EZH2 interface was assayed. Leave the specific binding assertion undecided pending the original data. |
| GO:0003677 DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Specify the demonstrated chromatin-associated DNA interaction. Reason: The mouse donor PMID23942234 shows Ezh2 ChIP in C2C12 cells; the DNA motif being analyzed belongs to YY1. Human PRC2 cryo-EM independently resolves EZH2 contacts with nucleosomal DNA. Chromatin DNA binding is a more informative supported term than unrestricted DNA binding, without transferring YY1 sequence recognition. Proposed replacements: chromatin DNA binding |
| GO:0003682 chromatin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Chromatin binding is a conserved EZH2 activity. Reason: PTHR45747 places the exact 746-residue human target PTN002505151 below the positive GO:0003682 IBD at PTN000768863. No target-path NOT assertion was found. The human source in WITH is valid descendant grounding, not circularity. Actual human PRC2 structures show direct EZH2–nucleosome contacts and independently support this inherited function. |
| GO:0003682 chromatin binding | IDA PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | ACCEPT | Summary: EZH2 associates with target chromatin in human cells. Reason: PMID:20154697 Figure5d and the corresponding Results report EZH2 ChIP enrichment at the DAB2IP promoter. This supports chromatin association; ChIP alone does not establish intrinsic sequence-specific DNA recognition. Supporting Evidence: |
| GO:0003682 chromatin binding | IEA GO_REF:0000120 | ACCEPT | Summary: Retain chromatin binding supported by orthologs and human target evidence. Reason: Both current mouse Q61188 and rat A0A8I6AHI4 records contain experimental chromatin-binding assertions as well as propagated records; they are not all independent experiments. The direct human PRC2 structural contacts in PMID33479123 and human ES-cell ChIP in PMID20064375 establish the target function independently. No claim is made to have read every donor experiment. |
| GO:0003714 transcription corepressor activity | IEA GO_REF:0000107 | ACCEPT | Summary: EZH2 functions as a catalytic transcriptional corepressor. Reason: The mouse donor carries PMID19026781 IDA. Actual repression assays and purified PRC2 chemistry distinguish EZH2 from the stronger SAM-independent chromatin compaction of EZH1. Human EZH2 also enhances CRY-dependent reporter repression in PMID16717091. GO:0003714 includes a chromatin-modifying corepressor recruited through DNA-binding regulators; it does not require EZH2 to recognize a specific DNA motif. |
| GO:0003714 transcription corepressor activity | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the conserved transcriptional corepressor function. Reason: The specified Q61188 donor has actual PMID19026781 experimental support, not only an electronic rule. PRC2-associated EZH2 methylation and human EZH2-dependent reporter repression support the corepressor function. The human reporter host is not evidence that every recombinant preparation in the donor paper was human, and EZH1-specific SAM-independent compaction is not assigned to EZH2. |
| GO:0003723 RNA binding | EXP PMID:35682829 The Disordered EZH2 Loop: Atomic Level Characterization by (... | MODIFY | Summary: Specify the tested long-noncoding RNA ligand class. Reason: PMID:35682829 measures NMR perturbations of an isolated EZH2 loop with HOTAIR1–140. The contact is weak and low-specificity, leaves the loop disordered and does not require a particular G-quadruplex fold. Together with purified human PRC2 binding to RepA/Hes1 antisense probes and isolated human EZH2 binding to Hes1 antisense RNA in PMID:21172659, this supports lncRNA binding as the more specific gene-level activity. It does not establish lncRNA sequence exclusivity, actual phosphorylation-dependent binding or equivalent behavior of all full-length products. Proposed replacements: lncRNA binding |
| GO:0003723 RNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Refine RNA binding to the independently tested lncRNA ligands. Reason: Current mouse provenance includes RNA-association experiments and a human-derived ISO; those versions remain separate. Independent PMID:21172659 tests purified human PRC2 from Sf9 cells with RepA/Hes1 antisense probes and Gtl2 RNAs, and identifies isolated human EZH2 as the subunit directly shifting Hes1 antisense RNA. Those direct assays support the more specific lncRNA-binding term, rather than inferring ligand identity from cellular RIP alone. The refinement does not assert exclusive recognition of lncRNAs or equal behavior of all five natural products. Proposed replacements: lncRNA binding |
| GO:0005515 protein binding | IPI PMID:11571280 Polycomblike PHD fingers mediate conserved interaction with ... | KEEP AS NON CORE | Summary: Retain the human PHF1 association as a non-core interaction. Reason: The original abstract explicitly reports human PHF1–EZH2 association, but the complete original Methods remain unavailable. Independent human HEK293T PHF1-complex purification in PMID:23142980 and exact BioPlex target records in PMID:33961781 support the pair. The Drosophila experiments are separate, and PHF1 histone recognition is not assigned to EZH2. |
| GO:0005515 protein binding | IPI PMID:16179254 The human tumor antigen PRAME is a dominant repressor of ret... | UNDECIDED | Summary: The specific EZH2-PRAME association cannot be verified from the accessible abstract. Reason: PMID:16179254 reports PRAME-dependent recruitment of Polycomb proteins to retinoic acid receptor targets, but the full original interaction data were inaccessible. This is compatible with EZH2 recruitment but does not establish the exact Q15910-P78395 assay or directness. Keep the experimental source undecided, not removed. |
| GO:0005515 protein binding | IPI PMID:16357870 The Polycomb group protein EZH2 directly controls DNA methyl... | KEEP AS NON CORE | Summary: Retain binding to DNMT1 without assigning DNA methyltransferase activity. Reason: The actual corrected Figure 2a of PMID:16357870 tests GST-EZH2 fragments with in-vitro-translated DNMT1; corrected Figure 2c provides endogenous HeLa co-IP. Full-length and N-terminal EZH2 constructs bind, while the tested C-terminal fragment does not. The main remains inaccessible, but its supplementary Methods and corrective figure were inspected. These data support an interaction, not DNA methylation by EZH2 or equivalence of its five natural products. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16357870 The Polycomb group protein EZH2 directly controls DNA methyl... | KEEP AS NON CORE | Summary: Retain the DNMT3B interaction as non-core binding. Reason: Corrected Figure 2a and the original supplementary Methods show GST-EZH2/DNMT3B pull-down; corrected Figure 2c shows endogenous HeLa PRC2/DNMT association. The published correction restores omitted lanes and states that the conclusions are unchanged. The accessible original materials support the pair despite unavailable main text; they do not make EZH2 a DNA methyltransferase. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16357870 The Polycomb group protein EZH2 directly controls DNA methyl... | KEEP AS NON CORE | Summary: Retain the DNMT3A interaction as non-core binding. Reason: The actual corrected GST-EZH2/translated-DNMT3A experiment and endogenous HeLa co-IP support this association. The recombinant and cellular preparations are distinct. Main-text access remains limited, and paper fragment coordinates are not projected onto every current EZH2 product. DNMT3A chemistry is not transferred to EZH2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17560333 Role of the polycomb repressive complex 2 in acute promyeloc... | MODIFY | Summary: Refine the tested native RARA interaction to nuclear receptor binding. Reason: PMID:17560333 reports weaker native RARA association in transfected human 293T cells, alongside stronger PML-RARA fusion association. Endogenous native RARA is not recovered in the tested U937/HL60 contexts, so the positive claim is conditional. RARA is an independently verified nuclear receptor; GO:0016922 captures the partner class without assigning receptor activity to EZH2 or claiming universal endogenous association. Proposed replacements: nuclear receptor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17560333 Role of the polycomb repressive complex 2 in acute promyeloc... | KEEP AS NON CORE | Summary: Retain the pathological PML-RARA association in its disease context. Reason: The actual human NB4/U937-PR9 original supports PRC2 association with PML-RARA, with a contribution from SUZ12. The source partner Q15156 identifies the fusion entry, not native PML. This interaction does not establish an autonomous EZH2 tethering activity, normal PML binding or natural-product equivalence; retain the supported generic association outside the core summary. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19734898 The histone variant macroH2A is an epigenetic regulator of k... | KEEP AS NON CORE | Summary: The curated EZH2-SUZ12 association is consistent with a core PRC2 complex. Reason: The supplied partner is SUZ12. Complete PMID:19734898 interaction experiments were inaccessible, but native human complex and reconstitution evidence in PMID:15385962 directly establishes the EZH2-SUZ12 association. Preserve the source row and retain generic protein binding as non-core; the informative role is PRC2 membership. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20075857 JARID2 regulates binding of the Polycomb repressive complex ... | KEEP AS NON CORE | Summary: The supplied SUZ12 interaction is consistent with PRC2 assembly. Reason: PMID:20075857 reports a JARID2-PRC2 complex in the abstract, while its detailed assays are access-limited. Independent native human and reconstituted EZH2-SUZ12 complexes in PMID:15385962 establish the biological association. Retain generic binding non-core without claiming to have verified this paper-specific assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20075857 JARID2 regulates binding of the Polycomb repressive complex ... | KEEP AS NON CORE | Summary: EZH2 associates with JARID2-containing PRC2. Reason: The PMID:20075857 abstract identifies a stable JARID2-PRC2 complex; independent human PRC2 structural/reconstitution evidence in PMID:29348366 and PMID:33479123 supports the association. Preserve the supplied JARID2 isoform identifier without inferring an isoform-exclusive interaction; generic binding is non-core and does not establish an isolated binary interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20543829 Role for the MOV10 RNA helicase in polycomb-mediated repress... | KEEP AS NON CORE | Summary: Retain the positive EZH2–SUZ12 assembly control. Reason: PMID:20543829 Figure 6a and the human 293T FLAG/co-IP Methods establish EZH2–SUZ12 association. Negative MOV10 results elsewhere in the same study are not evidence against this positive pair. Cellular complex recovery supports non-core generic binding, without proving purified binary affinity or testing all EZH2 products. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22009739 Corepressor protein CDYL functions as a molecular bridge bet... | MODIFY | Summary: Refine the CDYL interaction to transcription corepressor binding. Reason: The original reports endogenous human MCF7 CDYL–EZH2 co-IP and GST-CDYL/translated-EZH2 mapping, including CDYL residues 61–309 and EZH2 residues 329–522 in paper coordinates. CDYL is the non-DNA-binding chromatin corepressor/bridging partner, fitting GO:0001222. Its histone-reader and adaptor functions are not transferred to EZH2. Proposed replacements: transcription corepressor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22094255 Oxidative damage targets complexes containing DNA methyltran... | KEEP AS NON CORE | Summary: Retain EED association in the oxidative-stress PRC2 context. Reason: The recovered full original describes human NCCIT nuclear DNMT3B-associated PRC2, including EED2 and EZH2. Independent reciprocal human PRC2 IP in PMID:22439931 directly corroborates the pair. EED2 is a partner form, not an EZH2 isoform, and stress redistribution does not establish a separate binding-driven catalytic activity. |
| GO:0005515 protein binding | IPI PMID:22094255 Oxidative damage targets complexes containing DNA methyltran... | KEEP AS NON CORE | Summary: Retain the human DNMT1-associated complex interaction. Reason: The actual original includes the HCT116 hypomorphic FLAG-DNMT1 context and oxidative-stress-associated complexes. This is cellular association/fractionation evidence. The positive corrected HeLa/GST experiments in PMID:16357870 independently support the pair; neither source implies intrinsic DNA methylation by EZH2. |
| GO:0005515 protein binding | IPI PMID:22094255 Oxidative damage targets complexes containing DNA methyltran... | KEEP AS NON CORE | Summary: Retain DNMT3B association in human nuclear extracts. Reason: Recovered Methods/Results show DNMT3B IP of human NCCIT PRC2 components, including EZH2, with and without oxidative stress. Association and redistribution are supported, but purified binary affinity and equivalent activity of all current EZH2 products were not established. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22439931 Deconstruction of the SS18-SSX fusion oncoprotein complex: i... | KEEP AS NON CORE | Summary: Retain reciprocal human EED–EZH2 co-recovery. Reason: The actual supplementary Figure S6D and its pixels show reciprocal EED, EZH2 and SUZ12 IP from human SYO-1 cells with IgG controls. The positive complex association is distinct from the paper’s mouse models and SS18-SSX pathology. It does not itself establish a separate molecular activity for EZH2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22439931 Deconstruction of the SS18-SSX fusion oncoprotein complex: i... | KEEP AS NON CORE | Summary: Retain reciprocal human SUZ12–EZH2 co-recovery. Reason: Supplementary Figure S6D directly shows human SYO-1 EZH2/SUZ12 recovery in reciprocal PRC2 IPs. This supports cellular assembly binding; no autonomous binary affinity, universal disease response or all-product equivalence follows from that experiment. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22897849 ASXL1 mutations promote myeloid transformation through loss ... | KEEP AS NON CORE | Summary: Retain the EED interaction with an explicit independent human bridge. Reason: The source contains the curated EED–EZH2 context, while the operative passages inspected focus on ASXL1 association. Actual reciprocal human EED/EZH2 IPs in PMID:22439931 independently establish the pair. This does not claim inspection of an unidentified source-specific panel or assign ASXL1 activity to EZH2. |
| GO:0005515 protein binding | IPI PMID:22897849 ASXL1 mutations promote myeloid transformation through loss ... | KEEP AS NON CORE | Summary: Retain the human ASXL1–EZH2 association. Reason: The original human FLAG-ASXL1/EZH2 assays and endogenous SET2/UKE1 co-IP support association, including nuclease-treatment controls. These establish a protein-complex context, not a new autonomous EZH2 adaptor function or equivalent behavior of every natural product. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23142980 Molecular basis for H3K36me3 recognition by the Tudor domain... | KEEP AS NON CORE | Summary: Retain PHF1-containing human PRC2 assembly. Reason: Human HEK293T PHF1-complex purification and the PHF1 W41A/Y47A Tudor-mutant comparison support association with PRC2. PHF1 histone recognition is separate from EZH2 catalysis; mouse ESC and yeast-nucleosome experiments are not described as human binding assays. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23238014 CRL4B catalyzes H2AK119 monoubiquitination and coordinates w... | KEEP AS NON CORE | Summary: Retain SUZ12 association using independently inspected human evidence. Reason: The original CRL4B main remains inaccessible; its curated ChIP-associated record does not by itself resolve direct binding versus co-occupancy. Positive human EZH2/SUZ12 co-IP and reciprocal PRC2 IP in PMID:20543829 and PMID:22439931 independently support the pair. No CRL4B ubiquitin-transfer activity is assigned to EZH2. |
| GO:0005515 protein binding | IPI PMID:23455924 A Y2H-seq approach defines the human protein methyltransfera... | MODIFY | Summary: Refine the SUV39H1 pair to histone methyltransferase binding. Reason: Actual original Table S3 row 123 reports the EZH2/SUV39H1 Y2H pair, and Table S5 row 133 records positive orthogonal luminescence co-IP (Z-score 14.5). The supplementary Methods/table definitions were read although the complete main is inaccessible. SUV39H1 is an independently verified histone methyltransferase; GO:1990226 captures binding to that enzyme without transferring its H3K9 substrate specificity to EZH2. Proposed replacements: histone methyltransferase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23684459 Phosphorylation of EZH2 activates STAT3 signaling via STAT3 ... | MODIFY | Summary: Refine the STAT3 interaction to DNA-binding transcription factor binding. Reason: Actual human patient-derived glioblastoma stem-like cells show EZH2–STAT3 co-IP; differentiated cells and established lines differ. STAT3 is the DNA-binding transcription factor, so GO:0140297 describes the measured partner class. Cellular K180/S21/catalytic-mutant results are context-dependent and do not constitute a purified methylation-turnover assay or all-product comparison. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23684459 Phosphorylation of EZH2 activates STAT3 signaling via STAT3 ... | KEEP AS NON CORE | Summary: Retain SUZ12 association in the STAT3-associated PRC2 context. Reason: The original STAT3 IP recovers PRC2 components in the human glioblastoma model; it is not a purified EZH2/SUZ12 binary assay. Independent reciprocal human PRC2 IP in PMID:22439931 directly supports this pair. STAT3-dependent tumor phenotypes are not inferred from generic binding alone. |
| GO:0005515 protein binding | IPI PMID:24074865 Dnmt3L antagonizes DNA methylation at bivalent promoters and... | KEEP AS NON CORE | Summary: Retain the experimentally tested mouse Dnmt3L partner context. Reason: The author-proof original explicitly uses mouse Dnmt3L (Addgene 13356), mouse ESC IP and tagged mouse Dnmt3L in human HEK293 cells; it also describes recombinant GST-EZH2/FLAG-Dnmt3L binding. The source partner Q9CWR8 is correctly mouse. The human host does not change that species, and historical reagent sequence/current EZH2-product identity is not independently verified. These positive associations are retained with that boundary. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24074865 Dnmt3L antagonizes DNA methylation at bivalent promoters and... | KEEP AS NON CORE | Summary: Retain DNMT3B association under the Dnmt3L competition experiment. Reason: The actual author-proof Methods/Results show endogenous DNMT3B/EZH2 association in human HEK293 cells and reduction as transfected mouse Dnmt3L increases. This supports a context-dependent cellular interaction, not DNMT3B chemistry by EZH2 or a claim that the mouse competitor is a human protein. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24074865 Dnmt3L antagonizes DNA methylation at bivalent promoters and... | KEEP AS NON CORE | Summary: Retain DNMT3A association under the Dnmt3L competition experiment. Reason: Human HEK293 experiments in the recovered author proof report endogenous DNMT3A/EZH2 co-IP and competition by mouse Dnmt3L. The recombinant/ESC experiments are separate. The positive pair is retained as generic binding without a natural-product equivalence or DNA-methyltransferase claim. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24183680 Reduced H3K27me3 and DNA hypomethylation are major drivers o... | KEEP AS NON CORE | Summary: Retain SUZ12 binding with the original-access limit explicit. Reason: The K27M paper’s complete original experiment was not recovered. Actual independent human EZH2/SUZ12 co-IP in PMID:20543829 and reciprocal IP in PMID:22439931 establish the association, so it remains non-core. No universal mutant effect or source-specific assay detail is inferred from the title or abstract. |
| GO:0005515 protein binding | IPI PMID:24474760 O-GlcNAcylation regulates EZH2 protein stability and functio... | KEEP AS NON CORE | Summary: EZH2 associates with the O-GlcNAc transferase OGT. Reason: PMID:24474760 reports reciprocal tagged co-IP in293T, endogenous association and co-sedimentation with PRC2. OGT modifies and stabilizes EZH2; this does not confer OGT catalytic activity on EZH2. Retain the association as non-core rather than treating generic binding as its defining molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | KEEP AS NON CORE | Summary: Retain PHF1 association using independent human evidence. Reason: The source abstract describes human chromatin AP-MS, but the full main and target row were not recovered. Human PHF1-containing PRC2 purification in PMID:23142980 and exact BioPlex target records independently support the pair. No demethylase activity is assigned to EZH2 from discoveries elsewhere in this screen. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | KEEP AS NON CORE | Summary: Retain EED association with independent human support. Reason: The source-specific AP-MS target details remain unread. The pair is positively established by actual human reciprocal PRC2 IP in PMID:22439931 and BioPlex target records in PMID:33961781. These sources support generic complex association without pretending that the inaccessible original or every current EZH2 product was tested. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | KEEP AS NON CORE | Summary: Retain SUZ12 association with independent human support. Reason: The full original screen and exact target experiment were not recovered, but independently inspected human reciprocal PRC2 IP and BioPlex records establish the pair. This is a supported generic interaction, not evidence that EZH2 carries a separate demethylase function or that all natural products share an identical assay result. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Retain the sequence-identified human CEP63 screen interaction. Reason: Actual human ORFeome Y2H Methods describe autoactivation controls and pairwise retesting; Table S2G row 1667 contains EZH2/CEP63. S2C row 189 records MAPPIT/PCA/wNAPPA scores, without establishing that all three orthogonal assays are positive. No centrosomal function or current EZH2 product sequence is inferred solely from the interaction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25417162 ATRX directs binding of PRC2 to Xist RNA and Polycomb target... | UNDECIDED | Summary: The ATRX association is positive, but the exact human construct bridge remains unresolved. Reason: The full original reports purified ATRX–PRC2 binding and sequential assembly immunoprecipitation, alongside mouse Xist experiments. Its inspected Methods describe Sf9 FLAG/HA-ATRX and refer PRC2 preparation to prior work, leaving the human EZH2/ATRX reagent provenance unresolved. The human 293F immunoprecipitation is a macroH2A experiment and does not establish this exact pair. The listed corrections were not read, so their impact is not asserted. Retain UNDECIDED for these specific provenance and access limits while preserving the positive assembly evidence; neither a wrong-gene error nor absence of interaction is established. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: Retain PHF1 association without conflating source versions or BAC species. Reason: The recovered author thesis contains a 2014 under-review BAC-GFP/HeLa manuscript, whereas this annotation cites the final 2015 paper. Its Methods accommodate mouse BAC sequences, so host species alone is insufficient. Curated final-paper target records plus independent human PHF1 purification/BioPlex evidence support non-core binding; no preprint/final or product equivalence is asserted. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: Retain EED association with explicit final-paper access limits. Reason: The thesis supplies source-version AP-MS Methods but not verified final target BAC identity. Independent reciprocal human PRC2 IP and BioPlex target records establish the EED/EZH2 pair. The final original and complete bait metadata remain unavailable; this does not make a positive conserved assembly interaction incorrect. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: Retain SUZ12 association with explicit final-paper access limits. Reason: The actual author thesis and final curated pair record support the screen context; exact final bait sequence/species is not independently recovered. Human reciprocal PRC2 IP and BioPlex data establish the association separately. AP-MS does not establish direct binary contact or equivalence of the five current EZH2 products. |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | KEEP AS NON CORE | Summary: Retain PHF1 association in the human Polycomb AP-MS network. Reason: The July 7, 2016 author preprint reports human ORFeome/HEK293-cDNA baits, Strep–HA purification and PHF1-associated PRC2; the final-paper IntAct record supplies the exact pair. The final journal PDF and separate target score table remain unavailable, and some network interactions were rescued below initial thresholds. Independent human PHF1 evidence corroborates the association without claiming binary binding or preprint/final equivalence. |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | KEEP AS NON CORE | Summary: Retain EED association in the human Polycomb AP-MS network. Reason: The actually recovered author preprint’s Methods and PRC2 Results identify human-cell core-complex co-recovery; the exact final-paper curated pair is EED/EZH2. Final-version equivalence and target clone identity are unverified. Independent reciprocal human PRC2 IP supports this non-core association; AP-MS alone is not a purified binary assay. |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | KEEP AS NON CORE | Summary: Retain SUZ12 association in the human Polycomb AP-MS network. Reason: The accessible July 2016 preprint describes human baits and a PRC2 interaction network containing EZH2 and SUZ12. Final-paper target score data and exact clone identity remain unread. Independent reciprocal human PRC2 IP provides direct cellular corroboration, while the generic binding annotation remains distinct from an autonomous molecular activity. |
| GO:0005515 protein binding | IPI PMID:27728805 N-Myc Induces an EZH2-Mediated Transcriptional Program Drivi... | KEEP AS NON CORE | Summary: Retain SUZ12 association in the human N-MYC assembly context. Reason: Human prostate-model N-MYC IP recovers EZH2/SUZ12, with inhibitor-sensitive assembly. That co-recovery is not itself purified binary EZH2/SUZ12 binding; independently inspected reciprocal human PRC2 IP establishes the pair. The SET-deleted protein is engineered, and mouse tumor phenotypes are not treated as human binding experiments. |
| GO:0005515 protein binding | IPI PMID:27728808 Enhancing the Cytotoxic Effects of PARP Inhibitors with DNA ... | KEEP AS NON CORE | Summary: Retain the directly inspected DNMT3B-associated EZH2 recovery. Reason: Actual Supplementary Figure S1A shows DNMT3B IP from fractionated untreated or H2O2-treated human NCCIT nuclear extracts, with EZH2 recovery and IgG controls. The main PARP1/DNMT1 experiments are not substituted for this pair. The result supports complex association rather than intrinsic DNA methylation by EZH2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28229514 Mutations in genes encoding polycomb repressive complex 2 su... | KEEP AS NON CORE | Summary: The supplied EED association is a supported PRC2 interaction. Reason: PMID:28229514 examines PRC2 disease variants, but its original interaction data were inaccessible. Human EZH2-EED complex membership is independently established by native/reconstituted PRC2 in PMID:15385962 and structural work. Retain generic binding non-core, without claiming that every disease variant preserves the interaction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28229514 Mutations in genes encoding polycomb repressive complex 2 su... | KEEP AS NON CORE | Summary: The supplied SUZ12 association is supported by independent PRC2 evidence. Reason: The full PMID:28229514 experiments were inaccessible, although the abstract describes SUZ12/EED variants affecting PRC2 output. Native human and reconstituted EZH2-SUZ12 complexes in PMID:15385962 establish the association independently. Retain generic binding non-core and keep variant-specific results unverified. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29628311 A Family of Vertebrate-Specific Polycombs Encoded by the LCO... | KEEP AS NON CORE | Summary: EZH2 associates with PHF1-containing PRC2. Reason: The supplied O43189 partner is PHF1, verified against the official UniProt record. The detailed PMID:29628311 assay was inaccessible, but independent human PHF1-complex mass spectrometry and EZH2 co-IP in PMID:23273982 establish the association. Retain generic protein binding as non-core without claiming that this source-specific assay was inspected. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29909548 Molecular heterogeneity and CXorf67 alterations in posterior... | KEEP AS NON CORE | Summary: Retain the joint EZHIP/SUZ12 PRC2 association context. Reason: Human Daoy/U2OS EZHIP IP-MS and repeated Daoy SUZ12/EZH2 IPs support the reported assembly; EPD210FH cells provide another context. Both source supporting entities are preserved. Co-recovery does not define binary stoichiometry or prove that EZH2 has the partner’s inhibitory activity; detailed supplemental target tables were not independently inspected. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:30026490 Armadillo repeat containing 12 promotes neuroblastoma progre... | KEEP AS NON CORE | Summary: EZH2 associates with ARMC12 in an RBBP4-dependent complex. Reason: PMID:30026490 human neuroblastoma co-IP experiments show that RBBP4 depletion diminishes ARMC12-EZH2 association. This is a supported complex association, not evidence of direct isolated binary contact. Generic protein binding is retained as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:30510991 Disruption of FOXP3-EZH2 Interaction Represents a Pathobiolo... | MODIFY | Summary: Refine FOXP3 association to DNA-binding transcription factor binding. Reason: The original reports fresh human Treg proximity ligation and human FOXP3/EZH2 tagged co-IP/PLA in HEK293T. FOXP3 is the DNA-binding transcription factor, fitting GO:0140297. PLA is proximity, and the co-IP is cellular association; mouse Treg experiments, particular FOXP3 variants and unverified historical plasmid/current-product correspondence remain separate. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:30923826 EZHIP/CXorf67 mimics K27M mutated oncohistones and functions... | KEEP AS NON CORE | Summary: EZH2 associates with SUZ12 and EZHIP in inhibitory PRC2 complexes. Reason: PMID:30923826 reports tagged EZHIP co-IP with endogenous EZH2/SUZ12 in HEK293T cells, with C-terminal requirements. Preserve the multi-partner source context; co-IP establishes association and does not alone prove separate direct binary contacts. Generic binding is non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Retain the WT CEP63 interaction underlying the variant comparisons. Reason: Actual supplemental tables compare EZH2 alleles with the WT interaction: M439T/T1331C disrupts the CEP63 pair, whereas N640K/R288Q are non-disruptive. The source also records a PCA retest for the disrupted allele. These variant effects do not negate WT binding; source coordinate/accession labels are retained without projecting them onto all current products. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32051553 The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma... | MODIFY | Summary: Refine ZNF263 association to DNA-binding transcription factor binding. Reason: Human U251 ZNF263 IP/western in the original detects EZH2 although the initial MS hit list did not. ZNF263 is the DNA-binding regulator at the SIX3 promoter, so GO:0140297 describes the supported partner class. SUZ12 is negative in the tested co-IP and is not inferred positive from chromatin co-occupancy; ZNF263 DNA recognition is not transferred to EZH2. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the PHF1 association observed in both BioPlex cell contexts. Reason: Actual directed AP-MS records contain EZH2/PHF1 in human 293T and HCT116; HCT116 includes a PHF1 bait direction. Literal EZH2 Q15910-2 and PHF1 O43189-2 labels are dataset identifiers, not an independent historical clone alignment. Cellular co-recovery supports generic binding without proving direct contact or all-product equivalence. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the EED association observed in both BioPlex cell contexts. Reason: The actual human 293T/HCT116 directed-edge files contain EZH2/EED. Q15910-2 and O75530-2 are preserved as literal dataset accession labels. Human ORFeome/FLAG–HA Methods support AP-MS association, not individual-sequence verification of all current EZH2 products or purified binary affinity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the SUZ12 association observed in both BioPlex cell contexts. Reason: Exact directed-edge records in 293T and HCT116 contain EZH2/SUZ12, with human ORFeome/FLAG–HA AP-MS Methods. The source label Q15910-2 does not independently establish the sequence of the historical insert. This positive assembly interaction remains non-core generic binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | KEEP AS NON CORE | Summary: Retain the measured PHF1 edge in the breast-cell AP-MS network. Reason: The author-linked NDEx edge 1489 connects EZH2 and PHF1 and is explicitly marked public_ppi=false, distinguishing measured data from imported public associations. Tagged human ORFs were assayed in breast-cell contexts. The union network merges WT/mutant bait experiments; no exact target variant, direct affinity or natural-product equivalence is inferred. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | KEEP AS NON CORE | Summary: Retain the measured EED edge in the breast-cell AP-MS network. Reason: Author-linked NDEx edge 1491 is the measured EZH2/EED AP-MS edge, not an imported public network connection. The actual supplementary Methods specify human tagged ORFs and cell contexts. Differential network scores are not affinities, and merged mutant/WT data do not establish a unique current EZH2 product. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | KEEP AS NON CORE | Summary: Retain the measured SUZ12 edge in the breast-cell AP-MS network. Reason: The exact author-linked NDEx edge 1496 connects EZH2/SUZ12 with public_ppi=false. Human-cell AP-MS and measured-edge provenance support the pair; public connections among other nodes are not substituted. The assay remains cellular co-recovery, with no universal mutant or natural-product claim. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35016035 Identification and functional characterization of transcript... | KEEP AS NON CORE | Summary: Retain SUZ12 association despite the unrecovered source-specific target dataset. Reason: The full source and precise target proteomics experiment were not recovered from the bounded publisher/preprint routes. Independent human PRC2 co-IP and BioPlex target data positively establish EZH2/SUZ12 association. The study’s transcriptional-activator title does not itself assign activator activity to EZH2. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | MODIFY | Summary: Refine the AKT1 association to protein kinase B binding. Reason: The actual human-cell study reports AKT1-E17K-enhanced EZH2 association in GST pulldown/NanoPCA assays, and Data S1 Figure iii shows recovery with both WT and E17K AKT1. AKT1 is protein kinase B, fitting GO:0043422. Tables distinguish these positives from untested endogenous validation; no purified affinity, mutant-exclusive interaction or EZH2 isoform equivalence is claimed. Proposed replacements: protein kinase B binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:37553330 SNIP1 and PRC2 coordinate cell fates of neural progenitors d... | KEEP AS NON CORE | Summary: Retain SUZ12 association while distinguishing the mouse source experiment. Reason: The source’s neural-progenitor nuclear IP experiments are mouse, with PRC2 co-recovery and RBBP5 negative controls. Independent actual human reciprocal PRC2 IP and BioPlex records establish the conserved EZH2/SUZ12 association. This does not convert the mouse developmental phenotype into a human binding assay or infer all-product equivalence. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Retain the human AP-MS PHF1 association. Reason: The original uses C-terminal FLAG–HA human ORFeome baits in U2OS, with sequence/QC and CompPASS filtering. Exact target network evidence is retained separately. Imaging, SEC co-elution and predicted structures are distinct modalities, not automatically orthogonal confirmation of this pair. Independent human PHF1-complex/BioPlex evidence corroborates non-core binding; the published correction concerns a duplicated loss equation. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Retain the human AP-MS EED association. Reason: The target interaction belongs to the original human U2OS AP-MS network; exact node/edge provenance is recorded separately. Independent reciprocal human PRC2 IP corroborates the pair. This is complex co-recovery, not inferred direct binding from an imaging model, and the equation correction does not state a revision to these interaction data. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Retain the human AP-MS SUZ12 association. Reason: The original human ORFeome/U2OS AP-MS context and exact target network record support cellular association, independently corroborated by reciprocal human PRC2 IP. No imaging or structure-prediction output is treated as a separate measured binding test, and no current-product sequence equivalence follows from a bait accession label. |
| GO:0005634 nucleus | EXP PMID:14532106 EZH2 is downstream of the pRB-E2F pathway, essential for pro... | MODIFY | Summary: Refine the established nuclear location to a supported nucleoplasmic pool. Reason: The inspected PMID:14532106 passages concern expression regulation and tumor assays rather than a resolved nuclear-localization experiment. Independent human nuclear fractionation in PMID:19144645 supports the broad location. The correction PMID:38347304 withdraws only the SUZ12 E2F1(E132) control blot in Figure 1B, not the paper or an EZH2 localization result. Independent supported human HPA observations and native human Reactome entity 212298 (Q15910, modeled residues 1–746) establish a nucleoplasmic pool. This supports the finer localization without claiming exclusive residence, denying chromatin-associated pools, or resolving which of the five natural products was observed. Proposed replacements: nucleoplasm |
| GO:0005634 nucleus | EXP PMID:15231737 Silencing of human polycomb target genes is associated with ... | MODIFY | Summary: Refine the established nuclear location to a supported nucleoplasmic pool. Reason: PMID:15231737 maps endogenous EZH2 to repressed human promoter chromatin by ChIP. This establishes chromatin occupancy rather than discriminating soluble nuclear compartments, and PMID:19144645 independently supports a nuclear fraction. Independent supported human HPA observations and native human Reactome entity 212298 (Q15910, modeled residues 1–746) establish a nucleoplasmic pool. This supports the finer localization without claiming exclusive residence, denying chromatin-associated pools, or resolving which of the five natural products was observed. Proposed replacements: nucleoplasm |
| GO:0005634 nucleus | IBA GO_REF:0000033 | MODIFY | Summary: Refine valid nuclear inheritance to nucleoplasm. Reason: The positive nucleus IBD at PTN000768863 is ancestral to the exact human PTN002505151 leaf in PTHR45747; placement and self-WITH support are valid. Human HPA antibody/cell observations and the native human Reactome entity 212298 independently support nucleoplasm. The refinement does not dispute broad nuclear inheritance or establish which of the five shared-antigen products was imaged. The finer location is not an exclusive-residence claim and does not deny separately supported chromatin-associated pools. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000768863 · PTN000768863 SUPPORTS TRANSFER The positive GO:0005634 IBD is ancestral to exact human PTN002505151 in PTHR45747; the target MSA matches 746 residues and no path NOT assertion was found. The broader inheritance is valid. Independent target evidence supports the finer term; this is not a node-placement or donor-count objection. Proposed replacements: nucleoplasm Supporting Evidence: GO_REF:0000033 GO_REF:0000052 Reactome:R-HSA-212263 |
| GO:0005634 nucleus | IDA PMID:19144645 Dynamic Histone H1 Isotype 4 Methylation and Demethylation b... | MODIFY | Summary: Refine the established nuclear location to a supported nucleoplasmic pool. Reason: PMID:19144645 reports EZH2 in HeLa nuclear-pellet fractions and associated methyltransferase assays. Its actual EZH2 experiment remains positive despite the G9a-focused title; fractionation alone does not distinguish nucleoplasm from all other nuclear pools. Independent supported human HPA observations and native human Reactome entity 212298 (Q15910, modeled residues 1–746) establish a nucleoplasmic pool. This supports the finer localization without claiming exclusive residence, denying chromatin-associated pools, or resolving which of the five natural products was observed. Proposed replacements: nucleoplasm |
| GO:0005634 nucleus | IEA GO_REF:0000120 | MODIFY | Summary: Specify the supported nucleoplasmic location. Reason: The merged source combines mouse evidence with UniProt SL-0191 nucleus mapping. Human HPA supported antibody observations and Reactome entity 212298 itself specify nucleoplasm, providing independent target evidence for the finer location. Antigen sharing prevents product-specific localization, and no claim is made that all mouse nuclear studies were inspected. The finer location is not an exclusive-residence claim and does not deny separately supported chromatin-associated pools. Proposed replacements: nucleoplasm Supporting Evidence: GO_REF:0000120 GO_REF:0000052 Reactome:R-HSA-212263 |
| GO:0005634 nucleus | NAS PMID:29348366 Structures of human PRC2 with its cofactors AEBP2 and JARID2... | MODIFY | Summary: Refine the established nuclear location to a supported nucleoplasmic pool. Reason: The accessible abstract of human PRC2 structural study PMID:29348366 supplies context rather than a separate localization assay; its complete original remained unavailable. Inspected HeLa nuclear fractionation in PMID:19144645 independently supports the broad location. Independent supported human HPA observations and native human Reactome entity 212298 (Q15910, modeled residues 1–746) establish a nucleoplasmic pool. This supports the finer localization without claiming exclusive residence, denying chromatin-associated pools, or resolving which of the five natural products was observed. Proposed replacements: nucleoplasm |
| GO:0005634 nucleus | NAS PMID:35800061 PRC2, Chromatin Regulation, and Human Disease: Insights From... | MODIFY | Summary: Refine the established nuclear location to a supported nucleoplasmic pool. Reason: The secondary source PMID:35800061 places PRC2 in nuclear chromatin regulation, rather than conducting a new localization assay. Direct human fractionation in PMID:19144645 corroborates the broad nuclear location. Independent supported human HPA observations and native human Reactome entity 212298 (Q15910, modeled residues 1–746) establish a nucleoplasmic pool. This supports the finer localization without claiming exclusive residence, denying chromatin-associated pools, or resolving which of the five natural products was observed. Proposed replacements: nucleoplasm |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Human antibody evidence supports nucleoplasm. Reason: The current HPA record reports nucleoplasmic localization with supported CAB009589 and HPA029131 observations. Selected U-251MG and SiHa images were actually viewed alongside their antibody/cell annotations; neither selected composite displays a visible blue overlay. HPA029131 antigen matches all five source products, so the images support the gene-level location without identifying a particular product or a quantitative distribution. Supporting Evidence: GO_REF:0000052 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212222 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 212222 input 5084071 → component 212285 → EZH2 212298; the event recruits DNA methyltransferases, not intrinsic DNA methylation by EZH2. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-212222 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212252 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 212252 input set 5084084 → member 212285 → EZH2 212298; the alternative EZH1-containing branch is not substituted for this target route. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-212252 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212263 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 212263 catalyst activity 3211728 → active unit EZH2 212298; this is the H3K27 trimethylation reaction. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-212263 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212269 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 212269 input 212288 → component 5084071 → 212285 → EZH2 212298; DNMT DNA chemistry remains distinct from EZH2 histone chemistry. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-212269 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3240295 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 3240295 catalyst activity 3240298 → physical complex 212285 → EZH2 212298. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-3240295 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3240783 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 3240783 output EZH2 212298. Here EZH2 protein is the expression product of an E2F-controlled event, not the entity performing its own transcription. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-3240783 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3240957 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 3240957 input EZH2 212298, representing PRC2 assembly. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-3240957 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5638332 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 5638332 catalyst activity 5638319 → active unit EZH2 212298; Reactome histone residue numbering is retained without rewriting the source. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-5638332 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8954110 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 8954110 input 212285 → EZH2 212298 within the E2F6-associated assembly. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-8954110 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9614810 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 9614810 output 212285 → EZH2 212298 during the modeled HCMV chromatin transition. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-9614810 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9614816 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 9614816 input 212285 → EZH2 212298 during the modeled latent viral chromatin association. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-9614816 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9710490 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 9710490 catalyst activity 212303 → physical entity 212288 → 5084071 → 212285 → EZH2 212298. This GSDME promoter model does not make EZH2 a DNA cytosine methyltransferase. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-9710490 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9764930 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 9764930 input 212285 → EZH2 212298 in the CDH1 promoter complex. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-9764930 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9764932 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 9764932 catalyst activity 9815908 → active unit EZH2 212298 in the CDH1-associated histone reaction. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-9764932 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9909611 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 9909611 input 212285 → EZH2 212298 in the CD274 promoter model. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-9909611 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9909631 | ACCEPT | Summary: Retain the target participant’s modeled nucleoplasmic location. Reason: The actual target route is 9909631 input 9909625 → component 212285 → EZH2 212298 in the CD274 histone-methylation model. Entity 212298 is native human UniProt Q15910, modeled residues 1–746, and its own compartment is GO:0005654. This supports the location independently of the event title; it is not evidence for all natural products or every activity of neighboring participants. Supporting Evidence: Reactome:R-HSA-9909631 |
| GO:0005677 chromatin silencing complex | IEA GO_REF:0000107 | MODIFY | Summary: Identify the specific EZH2-containing silencing complex. Reason: The mouse donor PMID26658965 supports a PRC2-associated chromatin-silencing assembly; only selected original Results were recovered. Independent actual mouse/native and recombinant PRC2 work in PMID19026781 and human PRC2 structure in PMID33479123 establish the specific ESC/E(Z), or PRC2, complex. This identifies the demonstrated complex rather than treating every chromatin-silencing assembly as equivalent. Proposed replacements: ESC/E(Z) complex |
| GO:0005694 chromosome | IDA PMID:19734898 The histone variant macroH2A is an epigenetic regulator of k... | MODIFY | Summary: Chromatin is a more informative location than a whole chromosome. Reason: The cited macroH2A/PRC2 study PMID:19734898 concerns gene-associated chromatin rather than a distinct chromosome territory. Complete source-specific panels remain unavailable, while human EZH2 chromatin association is independently established by ChIP and structural evidence. Refine this broad location to chromatin without claiming the original chromosome annotation was false. Proposed replacements: chromatin |
| GO:0005721 pericentric heterochromatin | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain a conditional pericentric heterochromatin localization. Reason: PMID27892467 actually demonstrates Ezh2-eGFP recruitment to pericentric heterochromatin in mouse ES cells after Dnmt1 depletion, with Jarid2 dependence and engineered MBD–Ezh2 experiments kept distinct. The positive donor localization is context dependent; it does not establish constitutive native human occupancy. Retain this conditional location without promoting it to the main EZH2 compartment. |
| GO:0006325 chromatin organization | TAS PMID:8921387 Characterization of EZH1, a human homolog of Drosophila Enha... | UNDECIDED | Summary: The original source mapping for this chromatin-organization statement remains unverified. Reason: The PMID:8921387 abstract explicitly describes human EZH1 at17q21 rather than the current EZH2 locus. However, the full article was not accessible, and neither historical nomenclature nor an omitted EZH2 discussion can be resolved from the abstract alone. Leave this TAS source undecided; no wrong-gene accusation or removal is made. |
| GO:0006338 chromatin remodeling | IEA GO_REF:0000002 | ACCEPT | Summary: Histone-state modification supports chromatin remodeling. Reason: Current InterPro IPR045318 includes the target and maps this process together with histone methyltransferase activity. GO:0006338 encompasses changes in chromatin organization through histone modification and is not restricted to ATP-driven nucleosome sliding. Human PRC2 nucleosome recognition and EZH2-dependent methylation provide the relevant mechanism; EZH1-specific SAM-independent compaction is not substituted for it. |
| GO:0006355 regulation of DNA-templated transcription | TAS PMID:8921387 Characterization of EZH1, a human homolog of Drosophila Enha... | UNDECIDED | Summary: The source-specific support for this transcription-regulation statement is unresolved. Reason: The accessible PMID:8921387 abstract describes human EZH1, whereas EZH2 transcriptional regulation is independently well established. Preserve the source identity and leave its TAS mapping undecided until the complete original can be checked; biological plausibility does not verify a historical citation. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:18713946 MYC stimulates EZH2 expression by repression of its negative... | KEEP AS NON CORE | Summary: EZH2 supports proliferation in human Burkitt lymphoma cell lines. Reason: The original PMID:18713946 Methods and Results describe two human EZH2 shRNAs in Raji and Namalwa cells, with reduced cell numbers after knockdown. This is direct human-target evidence despite the upstream mouse MYC discovery, but it is a context-specific downstream phenotype rather than the core molecular activity. Supporting Evidence: |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: Retain repression of gene expression. Reason: The rat donor points to PMID22821416 IMP, whose operative experiment remains unavailable. Independently read human EZH2 reporter/rescue experiments in PMID16717091 and the PRC2 chromatin mechanism support negative regulation of expression. This acceptance uses independent target evidence and does not claim to verify the rat Schwann-cell experiment. |
| GO:0010718 positive regulation of epithelial to mesenchymal transition | IDA PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | KEEP AS NON CORE | Summary: EZH2 promotes EMT in the examined prostate cancer model. Reason: PMID:20154697 reports EMT after ectopic EZH2 and its prevention by DAB2IP reconstitution. This is a context-specific downstream consequence of epigenetic DAB2IP repression, not the defining molecular function of EZH2. Supporting Evidence: |
| GO:0016279 protein-lysine N-methyltransferase activity | IDA PMID:19144645 Dynamic Histone H1 Isotype 4 Methylation and Demethylation b... | ACCEPT | Summary: EZH2-associated complexes methylate protein lysine substrates beyond H3K27. Reason: PMID:19144645 detects H1.4 methylation in anti-EZH2 immunoprecipitates from human nuclear fractions. Activity and complex integrity depend on wash conditions. Retain broad protein-lysine methyltransferase activity to preserve this substrate context rather than replacing it exclusively with an H3K27 term; isolated EZH2 catalysis is not claimed. Supporting Evidence: |
| GO:0016279 protein-lysine N-methyltransferase activity | IDA PMID:25620564 Jarid2 Methylation via the PRC2 Complex Regulates H3K27me3 D... | ACCEPT | Summary: EZH2-containing PRC2 methylates a nonhistone protein substrate. Reason: PMID:25620564 directly tests PRC2 methylation of JARID2 at K116 using recombinant substrates, mutagenesis and mass spectrometry. Broad protein-lysine methyltransferase activity preserves this nonhistone chemistry. EED reads methylated JARID2; the reader activity is not assigned to EZH2, and mouse/fly experiments remain distinct from human-product evidence. Supporting Evidence: |
| GO:0016279 protein-lysine N-methyltransferase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Retain protein-lysine methyltransferase activity beyond one histone site. Reason: Current mouse provenance includes human-derived ISO records and a separate experimental source. Actual PMID25620564 demonstrates PRC2 methylation of nonhistone JARID2 K116, with EZH2/EED-dependent cellular methylation; PMID19144645 tests human HeLa EZH2 immunoprecipitates on H1.4. These positive substrate classes justify the broader term. Complex or immunoprecipitate activity is not presented as isolated EZH2 activity or as evidence for every natural product. |
| GO:0016279 protein-lysine N-methyltransferase activity | TAS Reactome:R-HSA-212263 | ACCEPT | Summary: Retain supported protein-lysine methylation while specifying this reaction in the evidence. Reason: R-HSA-212263 explicitly models H3K27 trimethylation and identifies native human EZH2 212298 as the active unit of catalyst activity 3211728. This supports the imported protein-lysine methyltransferase claim. Independently, human anti-EZH2 immunoprecipitates methylate H1.4 in PMID:19144645 and EZH2-containing PRC2 methylates JARID2 K116 in PMID:25620564. Retaining the broader activity consistently across these contexts preserves real substrate breadth; the H3K27-specific core still represents the principal reaction. None of these assignments makes isolated EZH2 sufficient or attributes EED reader activity to EZH2. |
| GO:0021766 hippocampus development | IEA GO_REF:0000107 | UNDECIDED | Summary: The hippocampal-development inference needs the original experimental context. Reason: The current rat donor assertion is IEP from PMID23932971, distinct from the paper’s IMP transcription and dendrite assertions. Available abstract/introductory material does not resolve how the expression observation establishes this developmental process, and operative full text was not recovered. Retain uncertainty rather than rejecting an unread curator-supported context or treating expression alone as a demonstrated developmental step. |
| GO:0030183 B cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain a supported B-cell developmental role. Reason: The exact mouse donor PMID23531880 perturbs YY1 and rescues with WT versus deltaREPO, while measuring Ezh2 locus occupancy; it is not an Ezh2 knockout. Independently read PMID12496962 directly deletes the Ezh2 SET region and demonstrates a cell-autonomous pro-B to pre-B defect with H3K27 changes. This supports a conserved developmental application of chromatin regulation without making EZH2 an immunoglobulin recombinase or claiming a human B-cell assay. |
| GO:0030335 positive regulation of cell migration | IDA PMID:35609316 EZH2 enhances proliferation and migration of trophoblast cel... | KEEP AS NON CORE | Summary: EZH2 promotes migration in the examined trophoblast cell lines. Reason: PMID:35609316 reports scratch/Transwell and EZH2 perturbation experiments in HTR-8/SVneo and JEG3 cells, with GADD45A depletion rescue. Retain the downstream cell-state phenotype as non-core and context-specific; it does not establish direct motility machinery activity by EZH2. Supporting Evidence: |
| GO:0031048 regulatory ncRNA-mediated heterochromatin formation | IGI PMID:23435381 A pseudogene long-noncoding-RNA network regulates PTEN trans... | ACCEPT | Summary: EZH2 contributes to an ncRNA-dependent repressive chromatin mechanism. Reason: PMID:23435381 shows PTEN derepression on EZH2 depletion and loss of EZH2/H3K27me3 promoter occupancy on PTENpg1 antisense depletion. These experiments support the curated ncRNA-mediated silencing process. The direct RNA co-IP described in the inspected passage is DNMT3A, so it is not recast as a purified EZH2-RNA interaction assay. Supporting Evidence: |
| GO:0031490 chromatin DNA binding | IDA PMID:19734898 The histone variant macroH2A is an epigenetic regulator of k... | ACCEPT | Summary: EZH2 can engage chromatin DNA as part of substrate recognition. Reason: The full PMID:19734898 assay was not accessible, so its exact assay details are not independently verified. Nevertheless, directly inspected human PRC2 structural evidence in PMID:33479123 identifies EZH2 contacts with nucleosomal DNA. Retain chromatin DNA binding on this independent grounding, without equating it with promoter-sequence discrimination. Supporting Evidence: |
| GO:0031490 chromatin DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Retain chromatin DNA binding. Reason: Current mouse assertions include actual PMID18483221 and PMID24137001 ChIP evidence as well as human-derived transfers. Direct human PRC2 structures independently place EZH2 SET/CXC/bridge-helix residues against nucleosomal DNA. This is positive chromatin DNA binding; partner motifs and RNA–DNA hybrids are not evidence of EZH2 sequence recognition. |
| GO:0031491 nucleosome binding | IDA PMID:33479123 JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1... | ACCEPT | Summary: EZH2 directly contacts the nucleosome substrate in human PRC2. Reason: PMID:33479123 human PRC2 structures identify EZH2 SET/CXC and bridge-helix contacts with nucleosomal DNA and the H3 tail. This supports nucleosome binding in a reconstituted complex; it is not promoter-sequence discrimination and does not establish identical binding for every alternative product. Supporting Evidence: |
| GO:0031491 nucleosome binding | IEA GO_REF:0000117 | ACCEPT | Summary: Nucleosome binding is supported by rule and target structure. Reason: The current ARBA00085892 rule matches the target through condition set 3: FunFam 2.170.270.10:FF:000001 and Primates. Actual human PRC2 structures resolve EZH2 interactions with the nucleosome, supplying direct target corroboration beyond the rule conditions. This does not equate all five natural products or the engineered accessory subunits used for structural preparations. |
| GO:0031507 heterochromatin formation | IBA GO_REF:0000033 | MODIFY | Summary: Refine supported heterochromatin formation to the facultative process. Reason: The GO:0031507 IBD at PTN000768863 is valid on the exact human target path; no loss or incorrect placement is alleged. PRC2-dependent H3K27 methylation and regulated silencing support the more specific facultative heterochromatin process, also independently represented in mouse/human ES-cell evidence. Conditional pericentric recruitment is retained separately rather than treated as the principal constitutive heterochromatin mechanism. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000768863 · PTN000768863 SUPPORTS TRANSFER The positive GO:0031507 IBD is ancestral to exact human PTN002505151 in PTHR45747; the target MSA matches 746 residues and no path NOT assertion was found. The broader inheritance is valid. Independent target evidence supports the finer term; this is not a node-placement or donor-count objection. Proposed replacements: facultative heterochromatin formation |
| GO:0031507 heterochromatin formation | IDA PMID:26581166 Linker histone H1.2 establishes chromatin compaction and gen... | MODIFY | Summary: Specify EZH2-dependent facultative heterochromatin formation. Reason: PMID:26581166 shows EZH2-dependent H3K27me3, H1.2 recruitment, chromatin FISH proximity and MNase resistance at repressed loci in human MCF7 cells; wild-type but not H689A EZH2 rescues the effects. This regulated H3K27-marked chromatin supports facultative heterochromatin formation, consistent with the more specific process retained for the IBA context. EZH2 performs methylation, while H1.2 supplies the associated reader/structural contribution; no intrinsic EZH2 compaction or constitutive heterochromatin mechanism is inferred. Proposed replacements: facultative heterochromatin formation Supporting Evidence: |
| GO:0031507 heterochromatin formation | NAS PMID:29348366 Structures of human PRC2 with its cofactors AEBP2 and JARID2... | MODIFY | Summary: Refine the supported Polycomb process to facultative heterochromatin formation. Reason: PMID:29348366 provides an abstract-level structural/NAS context; its full operative original remains unavailable. Independent human EZH2 depletion, wild-type versus H689A rescue, FISH and accessibility experiments in PMID:26581166 establish the H3K27-dependent repressive architecture. This supports the same facultative heterochromatin refinement as the other GO:0031507 contexts, without assigning the reader or compaction mechanisms of partner proteins to EZH2. Proposed replacements: facultative heterochromatin formation Supporting Evidence: |
| GO:0031507 heterochromatin formation | NAS PMID:35800061 PRC2, Chromatin Regulation, and Human Disease: Insights From... | MODIFY | Summary: Specify the facultative H3K27-dependent heterochromatin process. Reason: PMID:35800061 distinguishes H3K27-marked facultative chromatin from other heterochromatin types and separates EZH1-associated compaction from EZH2 methyltransferase activity. Human EZH2-dependent chromatin architecture in PMID:26581166 independently supports the more specific facultative process. This preserves the positive NAS participation claim without asserting intrinsic EZH2 compaction or equivalent function of every natural product. Proposed replacements: facultative heterochromatin formation |
| GO:0031509 subtelomeric heterochromatin formation | IGI PMID:9214638 Mammalian homologues of the Polycomb-group gene Enhancer of ... | UNDECIDED | Summary: The native human subtelomeric process is unresolved by the accessible evidence. Reason: The PMID:9214638 abstract positively reports human EZH2 restoration of repression in yeast mutants impaired in telomeric silencing, alongside a transgenic-fly assay. That result supports heterologous silencing capacity, but the inaccessible full original leaves the subtelomeric mechanism and native human participation unresolved. General human facultative heterochromatin evidence does not establish this narrower compartment-specific process. Preserve the curated IGI assertion and its partner context without calling the yeast result erroneous or treating absence of a human localization assay as proof of no function. Supporting Evidence: |
| GO:0031519 PcG protein complex | IEA GO_REF:0000107 | MODIFY | Summary: Specify PRC2 among Polycomb-group complexes. Reason: The exact mouse source PMID21874018 assays Ezh2 and Suz12 within the PRC2 group of chromatin-associated proteins. Independent actual native/reconstituted PRC2 experiments and human structure establish the ESC/E(Z) complex, distinguishing it from PRC1 and other PcG assemblies. The RNA RIP source does not establish direct binding of every assayed protein to every lincRNA. Proposed replacements: ESC/E(Z) complex |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | UNDECIDED | Summary: Estradiol-response context remains insufficiently inspected. Reason: The current rat source is PMID25088689 IEP. GO:0032355 can legitimately include altered gene expression in response to estradiol, so expression evidence is not inherently invalid. However, the operative original experiment was not recovered; the available abstract alone does not justify a confident target/response judgment. No negative activity or wrong-species claim is inferred from that access limit. |
| GO:0035098 ESC/E(Z) complex | IBA GO_REF:0000033 | ACCEPT | Summary: Retain conserved PRC2 membership. Reason: The positive GO:0035098 IBD at PTN005243577 lies on the verified PTN002505151 human path in PTHR45747. The exact 746-residue MSA target and absence of a path NOT assertion support inheritance; human self-WITH is valid. Native human Reactome PRC2 212285 and actual human PRC2 structure independently confirm membership. |
| GO:0035098 ESC/E(Z) complex | IDA PMID:15385962 Suz12 is essential for mouse development and for EZH2 histon... | ACCEPT | Summary: Human EZH2 is a PRC2/ESC-E(Z) complex subunit. Reason: PMID:15385962 reports co-fractionation of human HeLa EZH2, EED and SUZ12, anti-EZH2 immunoprecipitation and reconstitution of active EZH2-EED-SUZ12 complexes. This directly supports core complex membership; the separate mouse embryo phenotype is not the human assay. Supporting Evidence: |
| GO:0035098 ESC/E(Z) complex | IDA PMID:20075857 JARID2 regulates binding of the Polycomb repressive complex ... | ACCEPT | Summary: EZH2 belongs to the JARID2-associated PRC2 complex. Reason: PMID:20075857 provides a stable JARID2-PRC2 complex summary, with full source-specific experiments access-limited. Human PRC2 complex membership is independently established by the directly inspected native and reconstituted complexes in PMID:15385962 and human structural studies. |
| GO:0035098 ESC/E(Z) complex | IDA PMID:23104054 Phf19 links methylated Lys36 of histone H3 to regulation of ... | ACCEPT | Summary: Human EZH2 associates with PHF19-containing PRC2. Reason: PMID:23104054 purifies full-length human PHF19 complexes from293T cells and identifies EZH2, SUZ12, EED and RBBP4/7 by mass spectrometry and immunoblotting. Mouse ESC co-IP is a separate corroborating experiment. PHF19 Tudor-mediated H3K36 reading is not transferred to EZH2. Supporting Evidence: |
| GO:0035098 ESC/E(Z) complex | IDA PMID:23273982 An H3K36 methylation-engaging Tudor motif of polycomb-like p... | ACCEPT | Summary: Human EZH2 is recovered in PHF1-associated PRC2 complexes. Reason: PMID:23273982 reports PRC2 subunits in PHF1-associated complexes from293 cells and EZH2/SUZ12 co-IP. PHF1 Tudor-dependent chromatin retention is distinguished from PRC2 complex assembly, supporting the core complex annotation without assigning the PHF1 reader function to EZH2. Supporting Evidence: |
| GO:0035098 ESC/E(Z) complex | IDA PMID:24474760 O-GlcNAcylation regulates EZH2 protein stability and functio... | ACCEPT | Summary: EZH2 is present in a human PRC2 complex. Reason: PMID:24474760 reports EZH2 co-sedimentation with the other PRC2 subunits and disruption of complex integrity following OGT depletion. This supports core complex membership in the examined human cell systems. Supporting Evidence: |
| GO:0035098 ESC/E(Z) complex | IEA GO_REF:0000120 | ACCEPT | Summary: Retain PRC2 membership from converging source routes. Reason: Current ARBA00089504 condition set 1 matches the target FunFam and Mammalia, while the mouse donor includes experimental PRC2 studies and propagated records. Actual human PRC2 structure and the native Reactome assembly corroborate the target complex. These are distinct provenance routes, not a count of independent experiments. Supporting Evidence: GO_REF:0000120 Reactome:R-HSA-3240957 |
| GO:0035098 ESC/E(Z) complex | IPI PMID:29348366 Structures of human PRC2 with its cofactors AEBP2 and JARID2... | ACCEPT | Summary: EZH2 is a component of the human PRC2/ESC-E(Z) complex. Reason: PMID:29348366 reports human PRC2 structures with JARID2 and AEBP2, providing direct complex evidence. Independent reconstitution and human nuclear-complex experiments in PMID:15385962 support this same core complex membership. |
| GO:0035098 ESC/E(Z) complex | NAS PMID:35800061 PRC2, Chromatin Regulation, and Human Disease: Insights From... | ACCEPT | Summary: EZH2 is the catalytic subunit in an EZH2-containing PRC2 complex. Reason: The PRC2 review PMID:35800061 explicitly distinguishes EZH2/EZH1, EED, SUZ12 and RBBP4/7 core subunits from accessory subcomplexes. This NAS complex annotation agrees with the directly inspected human reconstitution and structural studies. |
| GO:0042054 histone methyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Retain broad histone methyltransferase activity. Reason: IPR045318 maps this activity and the current mouse record includes both experimental and human-derived annotations. Actual PMID19144645 measures H1.4 K26-directed methylation by anti-EZH2 immunoprecipitates from the HeLa nuclear pellet, separately from G9a experiments; human PRC2 H3K27 chemistry is independently established. H3K27 alone would not capture this broader measured substrate scope, although the H1.4 experiment is not isolated EZH2 catalysis. |
| GO:0042054 histone methyltransferase activity | IMP PMID:26694085 Weaver Syndrome-Associated EZH2 Protein Variants Show Impair... | ACCEPT | Summary: Retain histone methyltransferase activity across the supported histone substrates. Reason: PMID:26694085 tests reconstituted human wild-type and variant EZH2-PRC2 complexes with mixed core histones and, separately, H3-tail peptides. The positive wild-type assays support histone methyltransferase activity; their H3K27 substrate focus does not delimit the full gene-level scope. Independent PMID:19144645 reports H1.4 K26-directed activity in anti-EZH2 immunoprecipitates from the HeLa nuclear pellet, compared with IgG and substrate controls. H1.4 is a histone, so an H3K27-only replacement would lose this measured breadth. The H1.4 preparation is not isolated EZH2, and variant-dependent reductions in the 2016 assay are not generalized to all alleles or natural products. |
| GO:0042393 histone binding | IDA PMID:33479123 JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1... | ACCEPT | Summary: EZH2 binds the histone H3 substrate tail. Reason: PMID:33479123 directly resolves histone H3-tail engagement by the EZH2 catalytic module in human PRC2. Retain histone binding as a substrate-recognition component of its core enzymatic activity, distinct from the H3K27me3 reader function of EED. Supporting Evidence: |
| GO:0042752 regulation of circadian rhythm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain circadian transcriptional regulation as a contextual role. Reason: The current mouse donor is PMID16717091 IMP. The actual original distinguishes mouse liver ChIP/co-IP and NIH3T3 oscillations from human EZH2 overexpression in HeLa mouse-promoter reporters and human EZH2 rescue of mouse-specific siRNA effects in NIH3T3 cells. Those positive human-construct experiments support the conserved regulatory role without claiming a native human circadian time course. |
| GO:0042752 regulation of circadian rhythm | IMP PMID:16717091 The polycomb group protein EZH2 is required for mammalian ci... | KEEP AS NON CORE | Summary: Human EZH2 can support a conserved circadian repression mechanism. Reason: PMID:16717091 tests human EZH2 overexpression in HeLa mouse-promoter reporters and human EZH2 rescue of mouse-specific RNAi in NIH3T3 cells. Mouse liver chromatin assays and fibroblast molecular oscillations are separate evidence. Retain circadian regulation as non-core without claiming an experimentally demonstrated human organism rhythm phenotype. Supporting Evidence: |
| GO:0043021 ribonucleoprotein complex binding | IEA GO_REF:0000107 | MODIFY | Summary: Use lncRNA binding for the experimentally demonstrated ligand. Reason: The exact donor paper PMID:21172659 uses purified human PRC2 with RepA/Hes1 antisense probes and Gtl2 RNAs, and separately shows isolated human EZH2 shifting Hes1 antisense RNA. Mouse cellular RIP experiments are distinct. GO:0043021 requires binding an RNA–protein ligand complex; these direct assays establish contact with RNA. GO:0106222 captures the tested lncRNA ligand class more specifically than root-level RNA binding and agrees with the independently retained lncRNA context. It does not assert sequence exclusivity or transfer every mouse RIP interaction to human EZH2. Proposed replacements: lncRNA binding |
| GO:0043406 positive regulation of MAP kinase activity | IDA PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | KEEP AS NON CORE | Summary: EZH2 increases MAPK signaling through repression of DAB2IP. Reason: PMID:20154697 measures ERK-pathway activation in EZH2-expressing human prostate cells and suppression by DAB2IP reconstitution. Retain the regulatory phenotype as non-core; EZH2 is not a MAP kinase or a direct kinase activator in this experiment. Supporting Evidence: |
| GO:0043547 positive regulation of GTPase activity | IDA PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | MODIFY | Summary: Correct the regulatory sign to positive Ras signaling. Reason: PMID:20154697 Figure 5 and its Results show that EZH2 represses DAB2IP in human prostate epithelial cells, increases Ras-GTP and downstream signaling, and that DAB2IP reconstitution reverses those effects. DAB2IP is a Ras GTPase-activating protein: suppressing its GAP function does not mean increasing GTP hydrolysis. The measured signaling outcome supports GO:0046579, not positive regulation of GTPase catalytic activity. EZH2 performs upstream transcriptional repression rather than Ras hydrolysis or nucleotide exchange; this remains a contextual downstream role. The 2024 correction replaces a Figure 1g control micrograph and does not concern these Figure 5 experiments. Proposed replacements: positive regulation of Ras protein signal transduction Supporting Evidence: |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Retain chromatin DNA interaction without assigning another factor’s specificity. Reason: PMID20956546, the exact mouse donor, measures Ezh2 promoter occupancy by ChIP in CD4 T cells. The inspected sequence motifs and EMSA concern STAT6, not EZH2. Independent human PRC2 contacts directly support chromatin DNA binding; this narrower description of the measured interaction avoids transferring STAT6 sequence recognition to EZH2. Proposed replacements: chromatin DNA binding |
| GO:0045120 pronucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the conserved early-embryo pronuclear localization. Reason: Actual PMID12900441 Methods, Results and Figure 1 caption show native Ezh2 in mouse pronuclei, with maternal conditional depletion and antibody controls. This is positive ortholog evidence for an early-developmental location, not human embryo imaging or a demonstration for all current natural products. Preserve it as a contextual localization. |
| GO:0045202 synapse | IEA GO_REF:0000108 | UNDECIDED | Summary: The process-to-synapse inference lacks resolved source support. Reason: This annotation derives through GO_REF:0000108 from GO:0051932 rather than from a direct synapse image. The current rat experimental provenance for that GABAergic process is PMID27690696, whose operative full text was not obtained. Neither the upstream process context nor an independent target-specific synaptic localization was established here. Do not convert the access gap or unusual paper title into a wrong-gene verdict. |
| GO:0045814 negative regulation of gene expression, epigenetic | IDA PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | ACCEPT | Summary: EZH2 mediates epigenetic silencing of DAB2IP. Reason: Promoter ChIP, DAB2IP mRNA/protein reduction and DAB2IP reconstitution in PMID:20154697 establish a transcriptional-silencing mechanism upstream of the cancer phenotypes. This is consistent with EZH2 acting as the catalytic subunit of repressive PRC2. Supporting Evidence: |
| GO:0045814 negative regulation of gene expression, epigenetic | IMP PMID:24623306 A KRAS-directed transcriptional silencing pathway that media... | ACCEPT | Summary: EZH2 participates in epigenetic repression at human INK4-ARF promoters. Reason: PMID:24623306 shows EZH2 promoter occupancy in H9 hESCs and DLD-1 cells, but EZH2 depletion derepresses these genes in H9 rather than DLD-1. Retain epigenetic silencing with this functional-context distinction; occupancy alone is not equated with necessity in every cell type. Supporting Evidence: |
| GO:0045814 negative regulation of gene expression, epigenetic | TAS Reactome:R-HSA-212300 | ACCEPT | Summary: Retain epigenetic repression through the PRC2 pathway. Reason: R-HSA-212300 contains event 212263, whose catalyst 3211728 identifies EZH2 212298 as active unit for H3K27 trimethylation. This gives EZH2 a performing role in the epigenetic repression pathway, unlike its separate role as an expression output in R-HSA-3240783. Neighboring DNA methylation reactions remain assigned to their DNA methyltransferases. Supporting Evidence: Reactome:R-HSA-212300 |
| GO:0045892 negative regulation of DNA-templated transcription | IBA GO_REF:0000033 | ACCEPT | Summary: Retain conserved negative regulation of transcription. Reason: The positive GO:0045892 IBD at PTN000768863 is ancestral to the exact human leaf. No target-path NOT or divergence was found, and the self-WITH entry is valid experimental descendant grounding. Human EZH2 reporter/rescue evidence and PRC2 chromatin chemistry independently support the conserved repressive function. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:26581166 Linker histone H1.2 establishes chromatin compaction and gen... | ACCEPT | Summary: EZH2 methyltransferase activity supports transcriptional repression. Reason: In PMID:26581166, EZH2 depletion derepresses target genes and wild-type but not catalytic H689A EZH2 restores repression. These human-cell experiments provide direct support for a core chromatin-dependent transcriptional-silencing role. Supporting Evidence: |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:16179254 The human tumor antigen PRAME is a dominant repressor of ret... | ACCEPT | Summary: Negative regulation of transcription is an established EZH2 function. Reason: The PMID:16179254 abstract describes PRAME-mediated Polycomb repression, but the exact EZH2-dependent experiments were not accessible. Retain the broad function because direct human EZH2 transcriptional repression is independently established in PMID:20154697 and PMID:26581166; the PRAME-specific source mechanism remains explicitly unverified. |
| GO:0046976 histone H3K27 methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Retain conserved histone H3K27 methyltransferase activity. Reason: The positive GO:0046976 IBD at PTN000768863 lies on the verified human path, whose ungapped MSA exactly matches the 746-residue target. No loss is indicated. Actual human PRC2 substrate contacts and methylation experiments independently support H3K27 chemistry in the assembled complex; this is not proof of equal activity across all natural products. |
| GO:0046976 histone H3K27 methyltransferase activity | IDA PMID:15385962 Suz12 is essential for mouse development and for EZH2 histon... | ACCEPT | Summary: EZH2-containing PRC2 methylates histone H3K27. Reason: PMID:15385962 tests native human and reconstituted PRC2 histone methylation and identifies the requirement for EED/SUZ12, with RbAp48 stimulation. Retain the H3K27 activity without implying that isolated EZH2 is sufficient or that H1 methylation in the same study is absent. Supporting Evidence: |
| GO:0046976 histone H3K27 methyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Retain H3K27 methyltransferase activity from domain and ortholog evidence. Reason: The actual target contains IPR021654 and IPR044439, whose current mappings include H3K27 methyltransferase activity. The mouse provenance contains both experimental and propagated records. Actual human PRC2 chemistry supports the same site specificity independently; an incidental H3K37 spelling in an InterPro description is not adopted as a new substrate assignment. |
| GO:0046976 histone H3K27 methyltransferase activity | TAS Reactome:R-HSA-9764932 | ACCEPT | Summary: Retain the modeled EZH2 H3K27 methyltransferase activity. Reason: The actual R-HSA-9764932 catalyst activity 9815908 names EZH2 entity 212298 as active unit within the CDH1-associated PRC2/nucleosome assembly. The native target and catalytic role are explicit, rather than inferred from mere membership in a nearby complex. Preserve the source-specific histone chemistry without assigning DNA methylation to EZH2. Supporting Evidence: Reactome:R-HSA-9764932 |
| GO:0048387 negative regulation of retinoic acid receptor signaling pathway | IMP PMID:16179254 The human tumor antigen PRAME is a dominant repressor of ret... | UNDECIDED | Summary: The source-specific contribution of EZH2 to retinoic acid receptor repression remains unresolved. Reason: PMID:16179254 clearly demonstrates PRAME/RAR biology in its abstract, but full-text EZH2 perturbation and recruitment experiments could not be inspected. Do not transfer PRAME necessity directly to EZH2 or reject the curator from an incomplete abstract; leave this specialized signaling annotation undecided. |
| GO:0048468 cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain developmental regulation downstream of chromatin control. Reason: The current mouse PMID23531880 context is YY1 perturbation with Ezh2 chromatin recruitment, not direct Ezh2 deletion. Independent Ezh2 conditional deletion in PMID12496962 establishes a cell-autonomous developmental transition defect. This supports a contextual cell-development role while leaving the specific YY1 and EZH2 experimental interventions distinct. |
| GO:0051932 synaptic transmission, GABAergic | IEA GO_REF:0000107 | UNDECIDED | Summary: The GABAergic-transmission inference remains unresolved. Reason: Current rat GOA assigns PMID27690696 IMP, but the operative Methods/Results were not recovered. Available metadata and abstract do not establish the specific GABAergic process context. No independently inspected experiment here resolves that step; retain uncertainty rather than inferring misattribution from the title or treating a generic chromatin role as synaptic transmission. |
| GO:0070878 primary miRNA binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the reported pri-miRNA association as contextual RNA binding. Reason: Actual PMID24137001 reports Ezh2 association with pri-miR-208b in mouse cardiac material by RNA-ChIP. The separate synthetic RNA–DNA hybrid assay is not a purified EZH2-binding experiment. Independent purified human EZH2 RNA binding supports biochemical plausibility, while the particular pri-miRNA and cardiac context remain ortholog-derived and non-core. |
| GO:0071902 positive regulation of protein serine/threonine kinase activity | IDA PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | KEEP AS NON CORE | Summary: EZH2 indirectly increases serine/threonine kinase signaling. Reason: PMID:20154697 reports increased ERK and AKT signaling after EZH2 expression and suppression by DAB2IP reconstitution. Keep this measured context-dependent regulatory outcome separate from the core histone methyltransferase activity; no protein kinase activity of EZH2 is implied. Supporting Evidence: |
| GO:0090183 regulation of kidney development | IEA GO_REF:0000107 | UNDECIDED | Summary: Kidney-development regulation needs evidence beyond the inspected expression summary. Reason: The current rat donor PMID18467665 is IEP. Its operative full text was inaccessible, and the available expression summary does not resolve an EZH2-performed regulatory step in kidney development. This is an evidence-access limitation, not a claim that the curator’s full experimental context was wrong. |
| GO:0106222 lncRNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Retain direct long-noncoding RNA binding. Reason: The exact mouse donor PMID27618650 assays Chaer with a mouse Ezh2 insert in a human in-vitro translation system; the host system does not make the protein human. Independent PMID21172659 directly tests purified human EZH2/PRC2 with RepA and Hes1 antisense RNAs. This supports lncRNA binding while leaving Chaer-dependent targeting and the five natural products’ behavior separately bounded. |
| GO:0140718 facultative heterochromatin formation | IEA GO_REF:0000107 | ACCEPT | Summary: Retain facultative heterochromatin formation through PRC2. Reason: The current mouse source includes PMID20064375 and PMID20064376; the former was actually read and combines PRC2/Jarid2 chromatin evidence with a separate human ES-cell ChIP experiment. Conserved H3K27 methylation and regulated silencing fit the current facultative-heterochromatin definition. Jarid2 recognition and EZH1-specific compaction are not reassigned to EZH2. |
| GO:0140938 histone H3 methyltransferase activity | TAS Reactome:R-HSA-5638332 | MODIFY | Summary: Specify H3K27 within this histone H3 reaction. Reason: R-HSA-5638332 identifies native human EZH2 212298 as the active unit of catalyst activity 5638319. The event summary describes mono-, di- and trimethylation and its output is the MeK28-histone H3 set 5638329; it is not restricted to monomethylation or to the single trimethyl endpoint stated in R-HSA-212263. GO:0046976 specifies methyl transfer at the conventional H3K27 site within this broader histone-H3 reaction. The source uses histone K28 numbering. Retaining this site-specific refinement does not narrow the independently supported whole-gene protein-lysine activity or contradict the successive-transfer GO:0140951 catalytic core. Proposed replacements: histone H3K27 methyltransferase activity Supporting Evidence: Reactome:R-HSA-5638332 |
| GO:0140951 histone H3K27 trimethyltransferase activity | IDA PMID:22323599 Mutation of A677 in histone methyltransferase EZH2 in human ... | ACCEPT | Summary: Wild-type EZH2-PRC2 has H3K27 trimethyltransferase activity. Reason: PMID:22323599 directly assays five-component PRC2 on H3K27 methylation-state substrates. Wild-type retains activity on dimethylated H3K27, while Y641 and A677G variants alter substrate preference. Retain the wild-type catalytic function without generalizing mutant hypertrimethylation or remapping historical residue numbers to untested natural products. Supporting Evidence: |
| GO:0140951 histone H3K27 trimethyltransferase activity | IDA PMID:26581166 Linker histone H1.2 establishes chromatin compaction and gen... | ACCEPT | Summary: EZH2 catalytic activity produces H3K27me3 in human cells. Reason: PMID:26581166 combines EZH2 depletion with wild-type and H689A rescue and measures target-locus H3K27me3. The result supports established H3K27 trimethylation while distinguishing loss-of-function mutants and substrate-reader effects from native wild-type activity. Supporting Evidence: |
| GO:0140951 histone H3K27 trimethyltransferase activity | IDA PMID:30923826 EZHIP/CXorf67 mimics K27M mutated oncohistones and functions... | ACCEPT | Summary: EZH2-dependent H3K27 methylation is inhibited by an EZHIP peptide. Reason: PMID:30923826 directly assays inhibition of an EZH2 methyltransferase preparation by an extended EZHIP peptide and relates cellular EZHIP expression to H3K27me3 loss. The shorter motif and M406G controls delimit inhibition. Retain the established H3K27 trimethyltransferase function without claiming the commercial preparation tests all natural EZH2 products or a newly solved inhibitory structure. Supporting Evidence: |
| GO:0140951 histone H3K27 trimethyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Retain H3K27 trimethyltransferase activity with the rule-access limit explicit. Reason: ARBA00098061 returned 404, so its current condition sets were not inspected. The target UniProt record nevertheless explicitly carries RHEA:60292 and EC:2.1.1.356; the official enzyme reaction and native human Reactome active-unit model support H3K27 trimethylation. Acceptance rests on those positive routes, not on an invented reconstruction of the unavailable rule. Supporting Evidence: GO_REF:0000120 Reactome:R-HSA-212263 |
| GO:0140951 histone H3K27 trimethyltransferase activity | IMP PMID:28229514 Mutations in genes encoding polycomb repressive complex 2 su... | ACCEPT | Summary: EZH2-PRC2 has H3K27 trimethyltransferase activity. Reason: PMID:28229514 reports reduced H3K27 trimethylation for EED/SUZ12 variants in its abstract; detailed assay configurations were unavailable. The wild-type EZH2 function is independently established by the directly inspected biochemical and cellular studies, including PMID:22323599 and PMID:26581166. Do not reinterpret another subunit variant as an EZH2 variant. |
| GO:0140951 histone H3K27 trimethyltransferase activity | IMP PMID:30026490 Armadillo repeat containing 12 promotes neuroblastoma progre... | ACCEPT | Summary: EZH2 supports H3K27 trimethylation in human neuroblastoma cells. Reason: PMID:30026490 combines EZH2 depletion/rescue with H3K27me3 detection and a nuclear-extract histone-peptide chemiluminescent assay. These support the established catalytic activity in the ARMC12/RBBP4 context, while the extract assay is not presented as purified EZH2 acting alone. Supporting Evidence: |
| GO:0140951 histone H3K27 trimethyltransferase activity | TAS PMID:24474760 O-GlcNAcylation regulates EZH2 protein stability and functio... | ACCEPT | Summary: H3K27 trimethylation is a defining catalytic output of EZH2-PRC2. Reason: PMID:24474760 is used here as TAS background for EZH2 catalytic activity while directly studying its O-GlcNAc regulation. Independent biochemical evidence in PMID:22323599 and cellular depletion/rescue in PMID:26581166 substantiate the activity. OGT-dependent stabilization is not itself an isolated-EZH2 enzyme assay. |
| GO:1900006 positive regulation of dendrite development | IEA GO_REF:0000107 | UNDECIDED | Summary: Dendrite-development regulation remains source-limited. Reason: The current rat donor assigns PMID23932971 IMP, distinct from its IEP hippocampus annotation. Operative Methods/Results were not recovered, so the specific direction, perturbation and developmental context cannot be assessed reliably. Preserve uncertainty instead of converting the available transcriptional abstract into a complete dendrite assay or a negative verdict. |
| GO:1900016 negative regulation of cytokine production involved in inflammatory response | IEA GO_REF:0000107 | UNDECIDED | Summary: Inflammatory cytokine regulation remains source-limited. Reason: The current rat donor assigns PMID27690696 IMP. Its operative original remains inaccessible, and no independent inspected target experiment here resolves this specific negative cytokine-production process. The title and abstract are not used to overrule the experimental annotation. |
| GO:1902808 positive regulation of cell cycle G1/S phase transition | IMP PMID:18713946 MYC stimulates EZH2 expression by repression of its negative... | KEEP AS NON CORE | Summary: EZH2 supports G1/S progression in the examined lymphoma cells. Reason: PMID:18713946 reports an increased G1 fraction after human EZH2 knockdown in Raji and Namalwa cells, with matched protein and cell-number measurements. Retain the measured cell-cycle regulatory context as non-core; it does not make EZH2 a general cell-cycle engine. Supporting Evidence: |
| GO:1990841 promoter-specific chromatin binding | IDA PMID:24623306 A KRAS-directed transcriptional silencing pathway that media... | ACCEPT | Summary: EZH2 occupies promoter-associated chromatin in human cells. Reason: PMID:24623306 detects EZH2 ChIP enrichment at p14ARF, p15INK4B and p16INK4A promoters, with reduced occupancy after ZNF304 depletion. GO:1990841 refers to promoter-associated chromatin binding and does not require intrinsic DNA-motif recognition by EZH2. Supporting Evidence: |
| GO:1990841 promoter-specific chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the contribution to promoter-associated chromatin binding. Reason: The mouse donor retains a contributes_to assertion from PMID26658965; selected original Results identify PRC2-associated promoter occupancy, with full Methods still unread. Independent human ES-cell ChIP in PMID20064375 and direct human PRC2 DNA contacts support the target’s contribution to promoter-associated chromatin. GO:1990841 does not by itself establish intrinsic nucleotide-sequence discrimination by EZH2. |
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Download this section (compressed HTML)Q: Which RNA interactions alter PRC2 recruitment or catalytic output in human cells, and which reflect binding without a regulatory consequence?
Q: How do the five source-described EZH2 products differ in PRC2 assembly, H3K27 methylation-state preference and RNA binding?
Experiment: Compare sequence-verified human EZH2 products in matched PRC2 reconstitutions, confirming complex integrity and measuring methyl transfer separately on H3K27me0, me1 and me2 substrates. Test RNA binding and methyltransferase output with defined RNAs in parallel, then assess selected RNA-contact mutants in human-cell rescue experiments while controlling protein abundance, complex assembly and catalytic-site integrity.
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