This is an intake checkpoint, not a biological review. All 186 source contexts and the five source-declared products remain unchanged and PENDING. The saved genuine fetch and schema commands succeeded. The Falcon/perplexity-lite provider chain failed with the actual 403/401 outcomes; no synthetic provider report was created.
The normal acquisition union is 112 PMIDs, 18 Reactome caches and three PAINT auxiliaries. The seed cites 61 PMIDs and 17 Reactome records; unused acquisition records remain private inventory candidates. Final public dependency selection follows scientific review. All 282 protected preimages and all ordinary normal-cache bytes remain unchanged.
The source's historical alias EZH1 is distinct from current approved EZH1/HGNC:3526/Q92800. The broad captured RefSeq list contains two related proteins, YY1 NP_003394.1 and EED NP_003788.2, from NCBI comment links. The original records remain unchanged; exact locus traversal excludes them from EZH2's product inventory. Five UniProt VSP products match official FASTAs; no functional equivalence among them is inferred.
Raw extension and WITH-group structure are retained in the original and mapped separately because the normal TSV/seed representation omits or flattens them. This is a representation boundary, not a source defect or scientific action. The source partition keeps whole PMID groups together and remains unassigned pending ROOT acceptance.
The following entries preserve the source-review chronology verbatim. Earlier pending/access statements are historical checkpoints; later entries and the explicit independent access correction supersede them. The final integrated assessment is stated after the appendices.
No annotation decisions have been applied. The review owns 67 contexts in 30 intact PMID groups; the other lanes own binding-only and database groups. Only the exact blocks in the read ledger have been read. No figure pixels, supplements, whole-paper coverage, or product equivalence is implied.
PMID:19144645(https://pubmed.ncbi.nlm.nih.gov/19144645/) is not merely a G9a paper. Its actual Results describe EZH2 in HeLa nuclear-pellet fractions and H1.4 methylation in anti-EZH2 immunoprecipitates, distinct from G9a. The native complex preparation and stringent wash limitation matter; this is not purified isolated-EZH2 chemistry. The current broad lysine methyltransferase annotation must not be narrowed exclusively to H3K27 on the basis of this source, because H1.4 is its substrate context. Nuclear location is directly supported by the fractionation. Original cache blocks16–18,24,30–32,57 inspected.
PMID:25620564(https://pubmed.ncbi.nlm.nih.gov/25620564/) directly tests PRC2-mediated JARID2 K116 methylation. Recombinant JARID2 fragments, mutation and mass spectrometry identify K116; mouse ESC deletion and fly evidence establish separate cellular and comparative contexts. Methylated JARID2 engages EED to stimulate PRC2, so methyl-lysine reading is not assigned to EZH2. The broad protein-lysine activity preserves this nonhistone chemistry. Mammalian and fly PRC2 are mentioned in Methods; the inspected main text does not establish all constructs' precise sequence accession or equivalence of five human source products. Blocks22–25,28–32,45–49,77 inspected.
PMID:33479123(https://pubmed.ncbi.nlm.nih.gov/33479123/) reports reconstituted human PRC2 with full-length EZH2, engineered EED/SUZ12 and JARID2 fragments, produced in HighFive insect cells. The structure identifies direct EZH2 contacts with nucleosomal DNA and the H3 tail, including a bridge helix. This supports substrate nucleosome/histone engagement without making it sequence-specific promoter recognition. Xenopus recombinant and commercial human nucleosomes are distinguished. Coupled SAH assays measure aggregate methyltransferase activity; they do not independently resolve every methylation state. Blocks15–16,29,34,37,40–41 inspected.
PMID:26694085(https://pubmed.ncbi.nlm.nih.gov/26694085/) compares commercial reconstituted human wild-type and Weaver-associated EZH2–PRC2 complexes using core histones and separately described H3-tail peptide assays. The main assay establishes positive wild-type histone methylation and reduced variant activity under those conditions, not equivalence of all disease alleles or native cellular dosage. The common D185H variant also reduces activity in vitro but is expressly not sufficient to cause Weaver syndrome. Blocks19,26,37–38,41 inspected; supplementary measurements not read.
PMID:22323599(https://pubmed.ncbi.nlm.nih.gov/22323599/) measures wild-type and mutant five-component PRC2 on different H3K27 methylation states. Wild-type retains measurable activity on dimethylated substrate, whereas historical Y641 and A677G mutants have altered substrate preference. Hypertrimethylation of mutant-expressing cells is not silently generalized to wild-type function. The source's historical residue labels remain unremapped to the five current products. Blocks30,32,34,47 inspected; additional Methods and peptide-library supplement not read.
Access limitations: captured PMC pages for PMID:20154697(https://pubmed.ncbi.nlm.nih.gov/20154697/),29348366,9214638 are browser-check pages despite HTTP200; their Europe PMC fullTextXML alternatives returned500. They are not originals. PMID:30923826(https://pubmed.ncbi.nlm.nih.gov/30923826/) and15385962 captured actual original HTML; operative reading is pending. Normal PMID:20154697(https://pubmed.ncbi.nlm.nih.gov/20154697/) has an optimistic full-text flag but contains only abstract/discussion. Current metadata links corrections38383797 (20154697) and38347304 (14532106); their impact is not yet established. No retraction is inferred. The PMID:9214638(https://pubmed.ncbi.nlm.nih.gov/9214638/) abstract expressly describes human EZH2 expression in fly and yeast assays; this is not demonstrated human telomeric localization. PMID:8921387(https://pubmed.ncbi.nlm.nih.gov/8921387/) abstract explicitly describes human EZH1 at17q21, but full text has not been inspected and no removal is made from that fact alone.
Subsequent original-source inspection resolves the pending reads above. PMID:15385962(https://pubmed.ncbi.nlm.nih.gov/15385962/) human HeLa fractionation and anti-EZH2 immunoprecipitation support a nuclear PRC2 complex and histone methylation. SUZ12 depletion disrupts activity and EZH2 stability; Sf9 reconstitution identifies an active EZH2–EED–SUZ12 minimum, with RbAp48 stimulation. Human ORFs and separate mouse embryo phenotypes are distinguished. Histone H1 and H3 methylation are reported. Blocks 9,45–46,48–50,52,54–57,59,80–81,89–93 inspected; blocks91–93 explicitly reread after truncated output.
PMID:30923826(https://pubmed.ncbi.nlm.nih.gov/30923826/) tagged human HEK293T EZHIP co-immunoprecipitation captures endogenous EZH2/SUZ12, not an isolated binary binding assay. C-terminal301–503 supports association and inhibition; a21-residue peptide inhibits a commercial EZH2 assay whereas the shorter13-residue motif alone at10micromolar does not. M406G abolishes inhibition. The pocket mimic is a model using an existing structure, not a newly measured structure. Product equivalence is not established. Blocks35–36,41–42,51,53–54,56,58,61,63,65–66,68 inspected.
PMID:38383797(https://pubmed.ncbi.nlm.nih.gov/38383797/) is the correction to PMID:20154697(https://pubmed.ncbi.nlm.nih.gov/20154697/). Its actual publisher PDF text and rendered page1 were read: the authors replace an incorrect Ki-67 control micrograph in Figure1g using recovered original data. It does not retract the paper. PMID:38347304(https://pubmed.ncbi.nlm.nih.gov/38347304/) is the correction to PMID:14532106(https://pubmed.ncbi.nlm.nih.gov/14532106/). The complete actual publisher notice retracts the SUZ12 E2F1(E132) control blot in Figure1B because two lanes resemble one another and original scans are unavailable; the authors state the negative control does not alter conclusions. The paper itself is not retracted. These specific limitations must accompany the corresponding reference assessments; no unrelated annotation is rejected merely because a correction exists.
PMID:20154697(https://pubmed.ncbi.nlm.nih.gov/20154697/) actual BioC Results and Methods now read. Human prostate epithelial cells with ectopic EZH2 suppress DAB2IP and show promoter ChIP enrichment; DAB2IP reconstitution suppresses Ras/ERK/AKT/NF-kappaB activation and EMT. These are downstream, cancer-context regulation phenotypes, not direct GTPase or kinase catalysis by EZH2. The Ki-67 correction is limited to Figure1g; the EZH2-specific evidence is Figure5. Figure captions read, no original experimental image pixels. Human transgene product sequence is not resolved.
PMID:35682829(https://pubmed.ncbi.nlm.nih.gov/35682829/) uses a bacterially produced isolated EZH2 loop and in-vitro-transcribed HOTAIR1–140. NMR perturbations localize weak, low-specificity binding to Thr367–Ser375; the loop stays disordered. Mg-dependent RNA folding is distinguished from a necessary G-quadruplex recognition mechanism, and T345D is a phosphomimetic, not measured phosphorylation. This supports broad RNA binding, not HOTAIR-specific recruitment by every complete product.
PMID:23435381(https://pubmed.ncbi.nlm.nih.gov/23435381/) tests human PTENpg1 antisense-dependent repression: EZH2 depletion relieves PTEN repression, and antisense depletion reduces EZH2 and H3K27me3 at the PTEN promoter. The direct RNA co-IP in the inspected paragraph is DNMT3A, so do not present it as purified EZH2-RNA binding. The existing ncRNA-mediated chromatin-silencing process is supported by these perturbation and ChIP experiments.
PMID:24623306(https://pubmed.ncbi.nlm.nih.gov/24623306/) directly studies EZH2 at INK4-ARF promoters despite emphasizing ZNF304. Human H9 and DLD-1 ChIP shows EZH2 recruitment; ZNF304 depletion decreases occupancy. EZH2 depletion derepresses these genes in H9 but not DLD-1, so occupancy and functional dependence must remain distinct. Promoter-specific chromatin binding denotes genomic association and does not assert intrinsic recognition of a DNA sequence motif.
PMID:35609316(https://pubmed.ncbi.nlm.nih.gov/35609316/) supports context-specific migration in HTR-8/SVneo and JEG3 trophoblast lines using scratch/Transwell and expression perturbation. GADD45A depletion rescues EZH2-knockdown phenotypes; the p38 relationship differs from the prostate DAB2IP pathway. Retain as non-core, without treating migration as EZH2 enzymatic action or a universal response.
PMID:24474760(https://pubmed.ncbi.nlm.nih.gov/24474760/) shows tagged and endogenous human EZH2 association with OGT, PRC2 co-sedimentation, and S75 O-GlcNAc modification. OGT modifies EZH2, not the reverse. Human breast/kidney contexts are distinguished from different mouse/fly results explicitly discussed. PMID:30026490(https://pubmed.ncbi.nlm.nih.gov/30026490/) shows human neuroblastoma ARMC12 association with EZH2 depends on RBBP4, with nuclear-extract H3 peptide H3K27me3 readout and EZH2 depletion/rescue. Do not call this direct binary ARMC12–EZH2 contact or isolated-EZH2 catalysis.
PMID:23104054(https://pubmed.ncbi.nlm.nih.gov/23104054/) initial human293T PHF19 purification identifies EZH2/SUZ12/EED/RBBP4/7; separate mouse ESC experiments validate endogenous complexes. PMID:23273982(https://pubmed.ncbi.nlm.nih.gov/23273982/) human293 PHF1-associated complexes contain PRC2 components, with core assembly distinguished from PHF1 Tudor-dependent chromatin retention. Neither study assigns the PHF Tudor H3K36 reader activity to EZH2.
PMID:15231737(https://pubmed.ncbi.nlm.nih.gov/15231737/) human SW480 ChIP demonstrates EZH2 at repressed MYT1 and other PRC2 target promoters with H3K27me3, not H3K9me3. EZH2 is absent from the examined silenced pericentromeric HTF6 promoter, so do not claim constitutive/pericentromeric localization. PMID:26581166(https://pubmed.ncbi.nlm.nih.gov/26581166/) shows human MCF7 EZH2 depletion and wild-type versus H689A rescue affecting H3K27me3, H1.2 recruitment, gene repression, FISH distance and MNase accessibility. H1.2 is the H3K27me3 reader in this mechanism; EZH2 provides methylation-dependent structural regulation.
PMID:16717091(https://pubmed.ncbi.nlm.nih.gov/16717091/) actual original transcription resolves species: human EZH2 promotes mCRY-mediated mouse-promoter repression in HeLa and rescues mouse-specific EZH2-siRNA effects in NIH3T3 reporter assays. The liver co-IP/ChIP and long-term molecular oscillations are mouse experiments. This supports conserved clock regulation with human transgene evidence; it does not demonstrate a human organism circadian phenotype or intrinsic sequence-specific DNA binding. The original PDF download failed, but selected original article text was available through the web reader and saved separately.
PMID:18713946(https://pubmed.ncbi.nlm.nih.gov/18713946/) original human-target experiments were recovered via the web reader despite publisher PDF403. Two human EZH2 shRNAs in Raji and Namalwa Burkitt lymphoma lines reduce cell numbers and increase the G1 fraction, independent of the upstream mouse MYC discovery. Both proliferation and G1/S regulation are supported as non-core cancer-context effects, not restricted to mouse evidence. Read Methods human shRNAs, EZH2-knockdown Results and Fig6 caption; no pixels. The source discussion infers dual transcriptional activation/repression from target expression, but these perturbations do not alone establish direct transcription coactivator activity.
PMID:35800061(https://pubmed.ncbi.nlm.nih.gov/35800061/) is a review and is assessed as secondary context, not a new experimental study. Its discussion distinguishes EZH1 structural compaction from EZH2 methylation-dependent repression. PMID:29348366(https://pubmed.ncbi.nlm.nih.gov/29348366/) abstract and available original text establish human PRC2 structure with AEBP2/JARID2; the current NAS broad nuclear/repressive roles are independently grounded in the directly inspected human studies. Current data do not make every five-product equivalent.
Access-limited source boundaries: publisher pages for20075857 and19734898 expose abstracts and access options, not complete original Results. Primary requests for29628311 (university repository including API fallback),28229514 (Wiley),16179254 (Cell) returned403, and article discovery did not establish another complete original. Their abstracts are read; any target-specific evidence not independently established must remain UNDECIDED, without asserting wrong paralog or an omitted assay. PMID8921387 explicitly describes EZH1 in its abstract, but full-text context remains unavailable. PMID9214638 explicitly tests human EZH2 in fly/yeast, while direct native human telomeric localization remains unverified.
The functional lane now contains 67 manually reviewed source contexts. Official partner identity verification corrected an unsealed draft identification of O43189 to PHF1 before candidate construction. Two genuinely fetched correction-notice caches are added without altering any pre-existing source bytes. Other annotation lanes and core synthesis remain separate.
Direct human PRC2 contacts support chromatin DNA and nucleosome binding. Promoter occupancy does not by itself establish intrinsic nucleotide-sequence recognition: several donor experiments instead measure YY1/STAT6 motifs, H3K27me3 ChIP or a protein-free RNA–DNA hybrid. Purified human EZH2 RNA EMSA supports RNA binding, while an RNA–protein ligand complex was not demonstrated by that assay.
Broad substrate terms remain justified by distinct chemistry: H1.4 methylation was measured in HeLa anti-EZH2 immunoprecipitates, and PRC2 methylates JARID2 K116. Neither is described as an isolated-EZH2 assay. Source-specific H3K27 refinements coexist with those broader findings. EED’s methyllysine-reading role and EZH1-specific compaction are not assigned to EZH2.
Actual PAINT ancestry supports the conserved functions, including valid human self-WITH evidence. Human HPA observations and the native Reactome participant support nucleoplasm but do not resolve the five natural products. Current pathway models distinguish EZH2 as an active unit, a complex member and an expression output. Unread specific rat developmental, GABAergic and inflammatory contexts remain unresolved; no experimental assertion is rejected from its abstract or title alone. Detailed public sources and access limits are in the source guide.
The 53 assigned interaction contexts were reviewed individually across 31 complete PMID groups: 45 remain non-core, seven are refined to verified partner-specific binding terms, and the ATRX context remains unresolved at the exact human recombinant/correction boundary. Positive generic interactions are retained under the standing campaign instruction; association alone does not assign the partner’s chemistry or a new autonomous EZH2 activity.
Original-access work distinguishes recovered full main text, author proofs/preprints, supplementary-only evidence and inaccessible originals. Human PRC2/PHF1 experiments independently corroborate several recurring pairs whose exact source experiment remains inaccessible; each such reason identifies that bridge. PML-RARA remains a pathological partner, mouse Dnmt3L remains mouse in human hosts, and current database product labels are not historical clone-sequence proof. Original tables preserve both positive WT associations and variant-dependent losses.
All 186 source objects and five products remain exact; the 133 contexts assigned to other lanes remain PENDING in this partial candidate. The 31 reference assessments preserve existing identities/titles/findings and add no quotation. No core synthesis, whole-gene status conclusion or canonical change is part of this checkpoint. Immutable normal sources remain untouched. The public source guide records operative source/version and assay limits.
The earlier chronology statement that PMID:29348366 had available original text is superseded. The preserved responses are a PMC browser-check page and a BioC no-result response; the source-specific read was its abstract only. No original Methods, Results, figure pixels or supplements from this reference were verified. The existing NAS decisions retain independent primary support from PMID:20154697 and PMID:26581166 (repression), PMID:19144645 (nuclear localization), PMID:26581166 (chromatin architecture), and PMID:15385962 (PRC2 membership). The original chronology remains intact as a historical record; this correction changes access wording, not any annotation action, source, product, citation identity or cache byte.
All 186 imported contexts have accepted manual decisions: 81 ACCEPT, 69 KEEP_AS_NON_CORE, 21 MODIFY and 15 UNDECIDED. The three disjoint source-review sets contain 67 functional, 66 database and 53 interaction contexts; no PMID group is split between owners. All source fields and the five literal products are preserved. The reference list contains 108 identities: the 86 seeded references, 20 database donor references and two genuine correction notices. Compatible assessments of four shared references were explicitly united.
The only review-reason changes beyond that merge correct CDYL/EZH2 fragment attribution and narrow the ATRX provenance/access explanation; no action, evidence source, replacement term or supporting-reference list changes. PMID:29348366 remains abstract-only for source-specific inspection, with the independent primary support named above. Binding reference prose uses public paper/Methods/figure/table locators; the exact read ledger is retained privately. The source-specific descriptions, access flags and verified identity assessments are distinct.
The final citation and machine-source selection contains 105 files. The larger acquisition union, including 51 unselected private sources, remains byte-preserved. Five otherwise conflicting donor caches use the exact fixed-main versions after a complete metadata/body comparison; the genuine private versions remain preserved. No core synthesis, new annotation, quotation, status reclassification or canonical publication is part of this checkpoint. See the source guide for experimental and product boundaries.
Added a standalone biological description and two compact units: catalytic H3K27 methylation in PRC2/chromatin and direct RNA binding in the nucleoplasmic PRC2 context. The catalytic unit uses GO:0140951 with its explicit successive-methylation definition, rather than redundant specific-plus-parent methyltransferase units. Positive H1.4/JARID2 chemistry remains in the description and accepted reviews. EED reader activity and accessory targeting remain assigned to their performers. The RNA unit adds no process assertion or universal recruitment direction. The source guide records the selectively reread original Methods/Results and species, construct and assay boundaries (PMIDs 15385962, 22323599, 19144645, 25620564, 33479123, 26581166, 21172659 and 35682829).
All 186 reviewed/source objects, 108 references, five natural-product records and the selected 105-file dependency map remain exact. No annotation, quotation, status or cache edit is made. Targeted questions/experiments concern RNA consequences and product-specific PRC2 assembly and catalysis. The existing chronology and correction of the earlier PMID:29348366 access claim are retained verbatim. Ontology definitions and pure is_a plus is_a/part_of branches are captured separately; validation and finite preservation receipts belong to the private synthesis packet.
EZH2 methylation and partner recognition remain distinct. The catalytic core retains GO:0140951: its current definition explicitly covers three successive transfers from unmethylated H3K27 to H3K27me3. Wild-type PRC2 activity on the three starting methylation states and the different Y641/A677G preferences are measured in PMID:22323599 (Results accompanying Figures 3–4 and main Materials and Methods). H1.4 methylation in human anti-EZH2 immunoprecipitates and JARID2 K116 methylation by PRC2 preserve the broader protein-lysine activity across all four imported contexts (PMID:19144645, Figure 1E and Experimental Procedures; PMID:25620564, Figure 1 and Results). EED is the methyllysine reader, not EZH2.
The RNA core and broad RNA refinements now name lncRNA binding. Purified human PRC2 binds RepA/Hes1 antisense probes and Gtl2 RNAs, while isolated human EZH2 directly shifts Hes1 antisense RNA in PMID:21172659 (Figure 5 and protein-purification/RNA-assay Methods). PMID:35682829 measures an isolated EZH2 loop contacting HOTAIR1–140 (Results 2.4 and Methods 4.1–4.3). Weak, low-specificity contact does not establish lncRNA sequence exclusivity; it also does not demonstrate another RNA class. Mouse pri-miR-208b RNA-ChIP is not silently converted to a purified-human assay. RNA-dependent recruitment or catalytic regulation remains context dependent. The five natural products remain functionally distinct questions, not equivalent tested reagents.
In the DAB2IP system, EZH2 represses a Ras GAP and increases Ras-GTP signaling; this is not positive regulation of GTP hydrolysis (PMID:20154697, Figure 5 and corresponding Results/Methods). The imported process is therefore refined to positive regulation of Ras protein signal transduction. DAB2IP reconstitution is an important causal control. The correction PMID:38383797 replaces a Figure 1g control micrograph and does not correct the separate Figure 5 experiments. EZH2 contributes upstream repression, not Ras catalysis.
All four heterochromatin-formation contexts now specify the facultative H3K27-associated process. The human catalytic-mutant rescue, locus FISH and accessibility experiments support EZH2's methylation contribution while separating H1.2's reader/structural role (PMID:26581166, Figures 4–6 and main Methods). Conversely, the positive heterologous yeast result in the PMID:9214638 abstract does not resolve native human subtelomeric participation. Both the specific telomeric location and process remain undecided while the full original is unavailable; this is not a negative verdict on the yeast experiment.
The standalone description now includes the disease axis: tested Weaver-associated variants can reduce PRC2 activity, whereas lymphoma-associated SET variants alter methylation-state preference by distinct mechanisms (PMID:26694085, Results and methyltransferase-assay Methods; PMID:22323599, Figures 3–4). No uniform mechanism is assigned to every germline variant, and EED/SUZ12 variants in PMID:28229514 are not relabeled as EZH2 variants. Six concise reference findings and reference-only support make selected evidence discoverable without adding publication quotations. Earlier entries above remain the historical notebook; this appendix records the current interpretation.
The two histone-methyltransferase contexts now retain the broader activity consistently. The 2016 wild-type and Weaver-variant PRC2 assays use mixed core histones and separate H3-tail substrates; they do not erase the independent H1.4 activity measured in human anti-EZH2 immunoprecipitates. That preparation-level result remains distinct from autonomous isolated-protein catalysis. See PMID:26694085(https://pubmed.ncbi.nlm.nih.gov/26694085/), Materials and Methods and Figure 2, and PMID:19144645(https://pubmed.ncbi.nlm.nih.gov/19144645/), Experimental Procedures and Figure 1E.
All seven broad nuclear contexts now use the same evidence-backed refinement to nucleoplasm. Each reason retains its original assay or inference limit; the finer compartment comes from independent human HPA observations and the explicit native human Reactome participant. This describes a supported pool, not exclusive residence, and does not deny chromatin-associated EZH2. Shared-antigen observations do not resolve all five natural products. The existing chromatin and complex evidence remains intact.
Bare reference links now make the remaining positive non-core support queryable, including the DAB2IP-dependent signaling phenotypes. Seven access-limited undecided rows remain without newly manufactured support. The two core functions are biologically unchanged; their terms are written inline for readability. Earlier notes remain the historical journal rather than being reordered. No new quotation, annotation, source record, reference assessment or status calculation accompanies this clarification.