CHD4 (Mi-2beta) is an ATP-dependent chromatin remodeler that engages nucleosomal DNA and histones to change nucleosome positioning and accessibility. It is a remodeling subunit of CHD4-containing NuRD assemblies and also forms the ADNP/HP1-associated ChAHP complex. DNA-binding regulators and chromatin readers recruit these assemblies to selected genomic regions, where CHD4 supports context-dependent transcriptional repression and, in other settings, transcriptional competence. HDAC subunits provide the associated deacetylation activity. Nuclear CHD4 also supports local transcriptional control and homologous recombination at DNA lesions. Developmental consequences include regulation of erythroid gene expression and neuronal maturation. A smaller cytoplasmic and centrosomal pool associates with pericentrin, with behavior distinct from CHD3. Pathogenic CHD4 variants cause a neurodevelopmental disorder.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Retain context-dependent repression of RNA polymerase II transcription. Reason: The exact rat E9PU01 donor has IMP evidence from PMID:18456662. Its Schwann-cell experiments concern EGR2/NAB2 recruitment, a dominant-negative CHD4 construct and Id gene expression; the promoter antibody recognizes CHD3/4. Independent human CHD4 recruitment and repression studies support the biological transfer, without claiming that this rat assay tested human CHD4 or that the historical Ensembl mapping was reconstructed. Supporting Evidence: file:human/CHD4/CHD4-source-evidence.json |
| GO:0000724 double-strand break repair via homologous recombination | IMP PMID:25593309 Screen identifies bromodomain protein ZMYND8 in chromatin re... | ACCEPT | Summary: CHD4 performs chromatin-associated work supporting homologous recombination. Reason: Actual PMID:25593309 Fig.4D measures reduced DR-GFP repair after CHD4 depletion, Fig.4EβJ examines CHD4 damage recruitment under ZMYND8 perturbation, and Fig.6DβI links CHD4 to local transcriptional silencing and RAD51 loading at FokI lesions. CHD4 provides chromatin remodeling and regulatory work rather than strand-exchange chemistry. The AsiSI RAD51 experiment in Fig.5 is ZMYND8-depleted and is not recast as a CHD4 assay. |
| GO:0000781 chromosome, telomeric region | IDA PMID:25150861 NuRD-ZNF827 recruitment to telomeres creates a molecular sca... | KEEP AS NON CORE | Summary: Retain telomeric recruitment in the alternative-lengthening context. Reason: The authentic abstract, publisher figure descriptions and supplementary reverse co-IP context of PMID:25150861 describe ZNF827-mediated NuRD recruitment to ALT telomeres. Preserve the curated CHD4 IDA location; the full main experimental series and a CHD4-specific telomeric image were not independently inspected. This is context-dependent telomeric association, not constitutive residence at every telomere. Supporting Evidence: |
| GO:0000785 chromatin | HDA PMID:16217013 Heterogeneous nuclear ribonucleoprotein C1/C2, MeCP1, and SW... | ACCEPT | Summary: CHD4 occupies chromatin as a component of a remodeling assembly. Reason: The human K562 LARC preparation contains Mi2beta/CHD4 and binds globin regulatory chromatin in ChIP and complex-level DNA assays. Independent purified human CHD4βnucleosome structures directly establish chromatin substrate engagement. MARE recognition by the LARC assembly is not assigned as an intrinsic CHD4 sequence motif. |
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: Chromatin is a principal site of CHD4 activity. Reason: The original PAINT ancestral assertion is consistent with human CHD4 chromatin occupancy, purified nucleosome remodeling and structure. Historical PTN002473914 placement was not reconstructed; target self-evidence and descendant count are not weaknesses. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The curated ancestral source is retained; historical PAINT placement was not reconstructed. Independent target evidence supports biological applicability without donor-count or target-self-reference objections. |
| GO:0001221 transcription coregulator binding | IPI PMID:29795351 Activity-dependent neuroprotective protein recruits HP1 and ... | MODIFY | Summary: Refine ADNP association to DNA-binding transcription factor binding. Reason: PMID:29795351 establishes ADNP-directed sequence-specific chromatin recruitment and recombinant human ADNPβCHD4 association in Extended Data Fig.4. The official GO:0001221 definition describes binding a coregulator that does not itself bind DNA; ADNP supplies sequence-specific recognition in this source. GO:0140297 better describes the measured partner class without assigning ADNP motif recognition to CHD4. Proposed replacements: DNA-binding transcription factor binding |
| GO:0003677 DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: DNA engagement is intrinsic to CHD4 chromatin remodeling. Reason: The PAINT DNA-binding assertion is consistent with direct human CHD4 contacts to nucleosomal DNA in PMID:32543371 and purified remodeling in PMID:28977666. Nucleosomal DNA binding describes one substrate context; it does not invalidate the broader physical DNA engagement. No sequence-recognition motif or reconstructed historical ancestral placement is asserted. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The curated ancestral source is retained; historical PAINT placement was not reconstructed. Independent target evidence supports biological applicability without donor-count or target-self-reference objections. |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: DNA engagement is intrinsic to CHD4 chromatin remodeling. Reason: The InterPro IPR009462 mapping is consistent with the CHD4 motor and chromodomain contacts to DNA observed in the human nucleosome-bound structure (PMID:32543371). Retain broad DNA binding alongside the separate nucleosomal-substrate annotation; the mapping itself is not a direct binding experiment. |
| GO:0003677 DNA binding | TAS PMID:9326634 Characterization of the CHD family of proteins. | ACCEPT | Summary: DNA engagement is intrinsic to CHD4 chromatin remodeling. Reason: PMID:9326634 supplies historical family and domain context. Independent full-length human structural and biochemical studies (PMID:32543371; PMID:28977666) establish DNA engagement and nucleosome remodeling, supporting this broad TAS annotation without attributing a sequence-specific recognition motif to CHD4. |
| GO:0003682 chromatin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Retain chromatin binding as substrate engagement of the CHD4 motor. Reason: Human nucleosome structures and biochemical remodeling support chromatin recognition through combined DNA and histone contacts. The PTN002473914 annotation is retained without claiming an independent reconstruction of its ancestral placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The curated ancestral source is retained; historical PAINT placement was not reconstructed. Independent target evidence supports biological applicability without donor-count or target-self-reference objections. |
| GO:0003714 transcription corepressor activity | IDA PMID:33859416 ZNF410 represses fetal globin by singular control of CHD4. | ACCEPT | Summary: CHD4 contributes transcriptional corepression through chromatin-remodeling assemblies. Reason: PMID:33859416 tests CHD4-dependent fetal-globin repression in human erythroid cells, while independent ZIP/ZGPAT, TBX5 and ADNP recruitment experiments place CHD4 in complexes recruited by DNA-binding regulators. ZNF410 binds regulatory DNA of the CHD4 gene in the original paper; it is not thereby a demonstrated protein recruiter of CHD4 at globin. CHD4 supplies remodeling, not HDAC chemistry. |
| GO:0005515 protein binding | IPI PMID:10220385 Three proteins define a class of human histone deacetylases ... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: Human Jurkat FLAG-HDAC1 co-IP detects CHD4 in Fig.5B; the exact positive IntAct record agrees with the source. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: histone deacetylase binding |
| GO:0005515 protein binding | IPI PMID:17314511 Large-scale identification of c-MYC-associated proteins usin... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: The authentic abstract explicitly validates MYC association with CHD4; two exact human tagged-co-IP/TAP records preserve the MYC 143β158 interaction-region feature and 293T host. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: DNA-binding transcription factor binding |
| GO:0005515 protein binding | IPI PMID:19644445 ZIP: a novel transcription repressor, represses EGFR oncogen... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: Full original human HeLa ZIP/ZGPAT affinity purification, reciprocal co-IP and EGFR ChIP/reChIP support CHD4-containing NuRD recruitment. ZIP is the sequence-specific repressor; CHD4 is not assigned its DNA motif. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: DNA-binding transcription factor binding |
| GO:0005515 protein binding | IPI PMID:20693977 Regulation of DNA-damage responses and cell-cycle progressio... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: The full original U2OS study documents CHD4-associated NuRD and CHD4-dependent recruitment of HDAC1/MTA2 to damaged chromatin. Independent human CHD4βHDAC1 assays corroborate the exact partner; no HDAC catalysis is transferred. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: histone deacetylase binding Supporting Evidence: file:human/CHD4/CHD4-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:21258344 Chemoproteomics profiling of HDAC inhibitors reveals selecti... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: The exact original human K562 endogenous co-IP record supports CHD4βHDAC1 association; inhibitor chemoproteomics concerns the associated HDAC complex. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: histone deacetylase binding |
| GO:0005515 protein binding | IPI PMID:21555454 The Brd4 extraterminal domain confers transcription activati... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: Full human 293T tagged-fragment and endogenous reciprocal co-IP experiments detect CHD4 association with the BRD4 ET region. BRD4 is a chromatin-reading transcriptional coregulator. The paper resolves several BRD4 assemblies rather than one complex containing every recovered protein. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: transcription coregulator binding |
| GO:0005515 protein binding | IPI PMID:22720776 PHF6 interacts with the nucleosome remodeling and deacetylat... | KEEP AS NON CORE | Summary: PHF6 associates with CHD4-containing NuRD in human cells. Reason: PMID:22720776 explicitly reports PHF6 copurification with CHD4, HDAC1 and RBBP4 in HEK293T cells; its complete abstract supports the association although the original full experimental series remains uninspected. A more specific partner class is not settled: human PHF6 fragments directly bind double-stranded DNA in PMID:24554700 (Methods; Figures 6β7), whereas GO:0001221 defines cofactors that do not bind DNA directly. PHF6 also represses a GAL4 reporter and binds RBBP4 (Figure 9), so its regulatory role is real, but it should not be forced into that narrower binding class. Retain the positive generic association as non-core, without transferring PHF6 activity to CHD4. Supporting Evidence: PMID:22720776 PHF6 copurified with multiple constituents file:human/CHD4/CHD4-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:23752268 The functional interactome landscape of the human histone de... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: Human CEM HDAC affinity-MS uses negative controls and statistical filtering; the exact positive CHD4βHDAC1 IntAct record is preserved. Co-complex recovery does not require a purified binary-interface claim. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: histone deacetylase binding |
| GO:0005515 protein binding | IPI PMID:25150861 NuRD-ZNF827 recruitment to telomeres creates a molecular sca... | KEEP AS NON CORE | Summary: ZNF827-associated NuRD binding is retained in its ALT-telomere context. Reason: The authentic PMID:25150861 abstract and publisher reverse-coimmunoprecipitation description support ZNF827-associated NuRD at ALT telomeres. This positive association is retained as non-core. The inspected source does not resolve a narrower partner class, such as sequence-specific transcription factor or non-DNA-binding coregulator, for this interaction; a zinc-finger name alone is insufficient. The complete original target series remains uninspected, and neither an intrinsic CHD4 telomere-scaffold activity nor a direct binary interface is inferred. |
| GO:0005515 protein binding | IPI PMID:26859351 The Cardiac TBX5 Interactome Reveals a Chromatin Remodeling ... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: Full PMID:26859351 maps association of human CHD4 N-terminal constructs with mouse TBX5 in HEK293 cells and tests endogenous mouse cardiac NuRD. The original mouse partner P70326 is retained; the assay is not described as an all-human pair. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: DNA-binding transcription factor binding |
| GO:0005515 protein binding | IPI PMID:26949739 Identification of Human Neuronal Protein Complexes Reveals B... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: The full source describes replicated endogenous HDAC1 IP-MS from differentiated human SH-SY5Y cells. Its exact CHD4 entry in Table S5 was not independently recovered, so the original curated link is distinguished from direct same-partner corroboration in PMIDs:10220385 and 28977666. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: histone deacetylase binding Supporting Evidence: file:human/CHD4/CHD4-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:28977666 CHD3 and CHD4 form distinct NuRD complexes with different ye... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: Three exact co-IP records and one cellular colocalization record are retained separately. Human CHD4-GFP coimmunoprecipitates HDAC1 in Fig.1; colocalization alone is not treated as the binding proof. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: histone deacetylase binding |
| GO:0005515 protein binding | IPI PMID:30134174 Positive Regulation of Transcription by Human ZMYND8 through... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: Full human ZMYND8βCHD4 co-IP and purified pull-down experiments support association. ZMYND8 is a chromatin-reading transcriptional coregulator whose monomer/dimer context changes complex preference; CHD4 is not assigned ZMYND8 histone recognition or P-TEFb activity. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: transcription coregulator binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: Three exact positive AP-MS records from the original human 293T/HCT116 BioPlex context support CHD4βHDAC1 co-complex association. The selected cache contains only part of the full paper, and the literal records supply the target evidence. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: histone deacetylase binding |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: The selected OpenCell cache is flagged full but contains Introduction/Discussion without the complete target Results/Methods. The exact source-specific CHD4βHDAC1 row was not recovered here. Independent positive same-partner human co-IP and biochemical assays support the class refinement while preserving the original curator provenance and access limit. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: histone deacetylase binding Supporting Evidence: file:human/CHD4/CHD4-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Retain the supported association with a more informative partner class. Reason: The full U2OS AP-MS Methods use sequence-validated C-terminal HA-FLAG baits and confidence filtering. The exact original CHD4βHDAC1 network edge was not independently recovered, so independent same-partner human biochemical/co-IP evidence, rather than a generic screen description, supports the class refinement. The specific binding definition describes the supported partner class; it does not transfer the partner's catalytic activity or establish an additional core mechanism. Proposed replacements: histone deacetylase binding Supporting Evidence: file:human/CHD4/CHD4-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:9804427 Chromatin deacetylation by an ATP-dependent nucleosome remod... | MODIFY | Summary: Refine the supported pericentrin association to scaffold protein binding. Reason: The original PMID:9804427-to-mouse-pericentrin linkage was not located in the inspected human CHD/HDAC purification text. Independent full PMID:17626165 directly tests human CHD4 residues 1577β1912 with mouse pericentrin residues 1340β1756 and separately detects endogenous human association. Pericentrin supplies a centrosomal scaffold, so GO:0097110 describes the supported partner class. This does not assign scaffold activity to CHD4 or transfer the distinct CHD3 anchoring phenotype. Preserve the original mouse P48725 partner and citation, with the source-linkage gap explicit. Proposed replacements: scaffold protein binding |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding supplies the CHD4 remodeling motor. Reason: The conserved ATPase-domain mapping is directly corroborated by human CHD4 nucleotide-bound structure and ATP hydrolysis/remodeling assays. ATP binding is an integral substrate interaction rather than a separate biological role. |
| GO:0005634 nucleus | EXP PMID:17626165 Chromatin remodeling proteins interact with pericentrin to r... | ACCEPT | Summary: The nucleus is a principal compartment of CHD4 function. Reason: Human RPE1 immunofluorescence shows a large nuclear CHD4 pool alongside cytoplasmic and centrosomal signal; the latter does not negate nuclear location. Supporting Evidence: |
| GO:0005634 nucleus | EXP PMID:27616479 De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remode... | ACCEPT | Summary: The nucleus is a principal compartment of CHD4 function. Reason: Wild-type and patient-associated human CHD4 constructs show nuclear localization in Fig.3B, separately from their preserved HDAC1 association. Supporting Evidence: |
| GO:0005634 nucleus | EXP PMID:27732854 ZMYND8 Co-localizes with NuRD on Target Genes and Regulates ... | ACCEPT | Summary: The nucleus is a principal compartment of CHD4 function. Reason: The original abstract describes CHD4-containing NuRD on nuclear target genes and damage sites. Independent human imaging and endogenous nuclear preparations corroborate location without recasting the abstract as a complete body read. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: The nucleus is a principal compartment of CHD4 function. Reason: The PAINT location agrees with endogenous human nuclear imaging, nuclear extract purification and chromatin work; ancestral node history was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The curated ancestral source is retained; historical PAINT placement was not reconstructed. Independent target evidence supports biological applicability without donor-count or target-self-reference objections. |
| GO:0005634 nucleus | IDA PMID:28977666 CHD3 and CHD4 form distinct NuRD complexes with different ye... | ACCEPT | Summary: The nucleus is a principal compartment of CHD4 function. Reason: Human CHD4-tagged cell lines and imaging show nuclear distribution; the study distinguishes CHD4 from CHD3 and does not test both current splice products separately. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:33283408 Cross-linking mass spectrometry reveals the structural topol... | ACCEPT | Summary: The nucleus is a principal compartment of CHD4 function. Reason: Endogenous tagged CHD4 is recovered from human HeLa Kyoto nuclear preparations and cross-linked NuRD assemblies. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: The nucleus is a principal compartment of CHD4 function. Reason: The original mouse orthology and UniProt subcellular-location sources are preserved; direct human imaging independently supports the broad nuclear assignment. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Retain HPA-supported nucleoplasmic localization. Reason: The authentic HPA XML lists nucleoplasm as an enhanced main location. Actual A431 and U2OS antibody images were inspected and show nuclear signal with nucleolar exclusion. This is antibody-based localization, not an assay of a specific splice product or proof of molecular activity in every stained compartment. Supporting Evidence: GO_REF:0000052 file:human/CHD4/CHD4-source-evidence.json |
| GO:0005654 nucleoplasm | IDA PMID:22720776 PHF6 interacts with the nucleosome remodeling and deacetylat... | ACCEPT | Summary: Retain nucleoplasmic CHD4 localization in the PHF6/NuRD context. Reason: The authentic PMID:22720776 abstract explicitly places the PHF6 interaction with CHD4/HDAC1/RBBP4 in the nucleoplasm rather than nucleolus. Independent endogenous human nuclear data and HPA support this core compartment; the full original fractionation series was not independently inspected. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3769447 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "HDAC1:2-containing complex deacetylate histones" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6805650 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "MTA2-NuRD complex deacetylates TP53" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8943780 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "SALL4 recruits NuRD to PTEN gene" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9613213 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "NAB2 and CHD4 bind and repress EGR-mediated RRAD gene expression" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9613476 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "EGR2:NAB2 and CHD4 bind the ID2 and ID4 promoter regions" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9679787 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "HDAC1:2-containing complex binds HDAC2 Inhibitors" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9940468 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "CHD and CDK2AP subunits are recruited to NuRD" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9940477 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "Formation of ChAHP complex" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9940948 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "GATAD2A NuRD binds ZMYND8:ZNF532:ZNF592:ZNF687" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9941697 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "ZNF827 and NR2C2,NR2F2 recruit NuRD to telomeric chromatin" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9941704 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "NuRD deacetylates telomeric nucleosomes" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9941744 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "PHF6 binds NuRD" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9944091 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "NuRD hydrolyzes ATP to affect nucleosome organization" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9944092 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "NuRD deacetylates nucleosomes" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9944706 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "NuRD binds TCF19 at FBP1 gene" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9944712 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "NuRD binds TCF19 at G6PC gene" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9944714 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "NuRD binds TCF19 at PCK1 gene" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9944893 | ACCEPT | Summary: Retain the nucleoplasmic location represented by the curated event. Reason: The official event "NuRD binds Ikaros family member proteins" is assigned to the nucleoplasm and includes CHD4 or a CHD-containing assembly. This supports location of the represented complex; it does not assign deacetylase chemistry, drug binding or every recruiter's activity to CHD4. Independent human nuclear and chromatin evidence corroborates the compartment. |
| GO:0005737 cytoplasm | IDA PMID:17626165 Chromatin remodeling proteins interact with pericentrin to r... | KEEP AS NON CORE | Summary: Retain the smaller cytoplasmic/centrosomal CHD4 pool. Reason: Full PMID:17626165 directly detects endogenous human CHD4 in RPE1 cytoplasm and centrosomes and validates pericentrin association. CHD4 depletion increases centrosomal pericentrin in this study, whereas CHD3 depletion reduces pericentrin and CHD4 retention. The CHD3 anchoring mechanism is not transferred to CHD4; this contextual location is kept outside the nuclear remodeling core. Supporting Evidence: |
| GO:0005813 centrosome | IDA PMID:17626165 Chromatin remodeling proteins interact with pericentrin to r... | KEEP AS NON CORE | Summary: Retain the smaller cytoplasmic/centrosomal CHD4 pool. Reason: Full PMID:17626165 directly detects endogenous human CHD4 in RPE1 cytoplasm and centrosomes and validates pericentrin association. CHD4 depletion increases centrosomal pericentrin in this study, whereas CHD3 depletion reduces pericentrin and CHD4 retention. The CHD3 anchoring mechanism is not transferred to CHD4; this contextual location is kept outside the nuclear remodeling core. Supporting Evidence: PMID:17626165 fraction of CHD4 located at the centrosome |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the smaller cytoplasmic/centrosomal CHD4 pool. Reason: Full PMID:17626165 directly detects endogenous human CHD4 in RPE1 cytoplasm and centrosomes and validates pericentrin association. CHD4 depletion increases centrosomal pericentrin in this study, whereas CHD3 depletion reduces pericentrin and CHD4 retention. The CHD3 anchoring mechanism is not transferred to CHD4; this contextual location is kept outside the nuclear remodeling core. Supporting Evidence: |
| GO:0006338 chromatin remodeling | HDA PMID:16217013 Heterogeneous nuclear ribonucleoprotein C1/C2, MeCP1, and SW... | ACCEPT | Summary: Retain chromatin remodeling as performed CHD4 core work. Reason: CHD4 itself provides ATP-dependent nucleosome remodeling, demonstrated with purified human protein and supported by human structural substrate engagement. Original human K562 LARC restriction-accessibility experiments measure remodeling by the CHD4-containing complex, not isolated CHD4 sequence-specific DNA recognition. |
| GO:0006338 chromatin remodeling | IBA GO_REF:0000033 | ACCEPT | Summary: Retain chromatin remodeling as performed CHD4 core work. Reason: CHD4 itself provides ATP-dependent nucleosome remodeling, demonstrated with purified human protein and supported by human structural substrate engagement. PTN002473914 history was not reconstructed; direct target grounding is legitimate rather than circular. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The curated ancestral source is retained; historical PAINT placement was not reconstructed. Independent target evidence supports biological applicability without donor-count or target-self-reference objections. |
| GO:0006338 chromatin remodeling | IDA PMID:9790534 The dermatomyositis-specific autoantigen Mi2 is a component ... | ACCEPT | Summary: Retain chromatin remodeling as performed CHD4 core work. Reason: CHD4 itself provides ATP-dependent nucleosome remodeling, demonstrated with purified human protein and supported by human structural substrate engagement. The full original Cell paper purifies human HeLa NuRD, distinguishes Mi2beta from Mi2alpha by peptide sequences and measures ATP-dependent nucleosome accessibility in Figs.3β4. Its HDAC and remodeling reactions are separate activities. |
| GO:0006338 chromatin remodeling | IEA GO_REF:0000120 | ACCEPT | Summary: Retain chromatin remodeling as performed CHD4 core work. Reason: CHD4 itself provides ATP-dependent nucleosome remodeling, demonstrated with purified human protein and supported by human structural substrate engagement. |
| GO:0008270 zinc ion binding | TAS PMID:7560064 Molecular analysis of a major antigenic region of the 240-kD... | KEEP AS NON CORE | Summary: Retain structural zinc binding by the CHD4 PHD fingers. Reason: The early sequence/antigen source identifies zinc-finger regions, while independent human CHD4 structural analysis establishes PHD architecture. This is structural metal binding, not a separate zinc-dependent catalytic function. The scanned full 1995 article was not completely read. |
| GO:0010629 negative regulation of gene expression | IDA PMID:33859416 ZNF410 represses fetal globin by singular control of CHD4. | ACCEPT | Summary: CHD4 contributes to repression of gene expression. Reason: The original human erythroid experiments identify CHD4-dependent fetal-globin repression, including CHD4 perturbation and CHD4 regulatory-element effects. Independent recruited remodeling complexes establish performed regulatory work; the broad term is retained as core coverage rather than replaced merely because a more specific repression assertion also exists. |
| GO:0010629 negative regulation of gene expression | IGI PMID:33301730 ZNF410Β Uniquely Activates the NuRD Component CHD4 to Silence... | ACCEPT | Summary: Retain CHD4-dependent repression downstream of ZNF410-controlled expression. Reason: In human HUDEP-2 cells, CHD4 re-expression in ZNF410-deficient cells almost completely restores gamma-globin silencing and most transcript changes (Fig.3EβH). This is genetic rescue evidence for CHD4 regulatory work; ZNF410 binds the CHD4 gene, not a demonstrated CHD4 protein interface at globin. Supporting Evidence: PMID:33301730 almost completely restored the silencing of Ξ³-globin |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | UNDECIDED | Summary: The exact membrane-fraction target evidence remains unresolved. Reason: The original study surveys a membrane-enriched preparation of human NK-like YTS cells. Its CHD4-specific target row and fraction/topology evidence were not recovered in this audit. GO:0016020 includes attached proteins as well as embedded proteins, so CHD4's nuclear prominence does not disprove the annotation. Retain the experimental source object and leave the assertion undecided rather than reject it from an abstract. Supporting Evidence: |
| GO:0016581 NuRD complex | IBA GO_REF:0000033 | ACCEPT | Summary: Retain CHD4 membership in NuRD. Reason: Human CHD4-containing NuRD is established by native purification, cellular co-IP and cross-linking studies. CHD4 supplies remodeling, whereas HDAC1/2 supply deacetylation. CHD3 and CHD4 need not coexist in a single NuRD particle. The PTN000085004 history was not reconstructed; target self-evidence is expected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000085004 UNRESOLVED The curated ancestral source is retained; historical PAINT placement was not reconstructed. Independent target evidence supports biological applicability without donor-count or target-self-reference objections. |
| GO:0016581 NuRD complex | IDA PMID:19644445 ZIP: a novel transcription repressor, represses EGFR oncogen... | ACCEPT | Summary: Retain CHD4 membership in NuRD. Reason: Human CHD4-containing NuRD is established by native purification, cellular co-IP and cross-linking studies. CHD4 supplies remodeling, whereas HDAC1/2 supply deacetylation. CHD3 and CHD4 need not coexist in a single NuRD particle. The original ZIP experiment recovers Mi2/CHD4-containing NuRD; independent human CHD4-tagged preparations strengthen target identity. |
| GO:0016581 NuRD complex | IDA PMID:33283408 Cross-linking mass spectrometry reveals the structural topol... | ACCEPT | Summary: Retain CHD4 membership in NuRD. Reason: Human CHD4-containing NuRD is established by native purification, cellular co-IP and cross-linking studies. CHD4 supplies remodeling, whereas HDAC1/2 supply deacetylation. CHD3 and CHD4 need not coexist in a single NuRD particle. Endogenous human CHD4 C-terminal contacts connect to the GATAD2-containing NuRD assembly; pooled cross-links do not establish every subunit alternative in one particle. |
| GO:0016581 NuRD complex | IEA GO_REF:0000120 | ACCEPT | Summary: Retain CHD4 membership in NuRD. Reason: Human CHD4-containing NuRD is established by native purification, cellular co-IP and cross-linking studies. CHD4 supplies remodeling, whereas HDAC1/2 supply deacetylation. CHD3 and CHD4 need not coexist in a single NuRD particle. The literal mouse donor and ARBA source remain unchanged; direct human complexes independently support applicability. |
| GO:0016581 NuRD complex | NAS PMID:16428440 MBD2/NuRD and MBD3/NuRD, two distinct complexes with differe... | ACCEPT | Summary: Retain CHD4 membership in NuRD. Reason: Human CHD4-containing NuRD is established by native purification, cellular co-IP and cross-linking studies. CHD4 supplies remodeling, whereas HDAC1/2 supply deacetylation. CHD3 and CHD4 need not coexist in a single NuRD particle. Original human 293-cell MBD2/MBD3 purifications identify Mi2beta; the authors explicitly left CHD3/CHD4 co-residence unresolved, later addressed by PMID:28977666. |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATP hydrolysis is directly established for human CHD4. Reason: Purified human CHD4 hydrolyzes ATP, and ATP-dependent nucleosome repositioning is measured separately. Current GO:0016887 permits retention of hydrolysis alongside an overall ATP-dependent activity; the integrated motor is summarized by GO:0140658. The original IBA source remains unchanged. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The curated ancestral source is retained; historical PAINT placement was not reconstructed. Independent target evidence supports biological applicability without donor-count or target-self-reference objections. |
| GO:0016887 ATP hydrolysis activity | IDA PMID:28977666 CHD3 and CHD4 form distinct NuRD complexes with different ye... | ACCEPT | Summary: ATP hydrolysis is directly established for human CHD4. Reason: Purified human CHD4 hydrolyzes ATP, and ATP-dependent nucleosome repositioning is measured separately. Current GO:0016887 permits retention of hydrolysis alongside an overall ATP-dependent activity; the integrated motor is summarized by GO:0140658. The original IDA source remains unchanged. Supporting Evidence: PMID:28977666 CHD4 as the motor subunit |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000116 | ACCEPT | Summary: ATP hydrolysis is directly established for human CHD4. Reason: Purified human CHD4 hydrolyzes ATP, and ATP-dependent nucleosome repositioning is measured separately. Current GO:0016887 permits retention of hydrolysis alongside an overall ATP-dependent activity; the integrated motor is summarized by GO:0140658. The original IEA source remains unchanged. |
| GO:0016887 ATP hydrolysis activity | TAS Reactome:R-HSA-9944091 | ACCEPT | Summary: ATP hydrolysis is directly established for human CHD4. Reason: Purified human CHD4 hydrolyzes ATP, and ATP-dependent nucleosome repositioning is measured separately. Current GO:0016887 permits retention of hydrolysis alongside an overall ATP-dependent activity; the integrated motor is summarized by GO:0140658. Reactome explicitly assigns NuRD ATP hydrolysis to CHD components, not the HDAC enzymes. |
| GO:0031492 nucleosomal DNA binding | HDA PMID:16217013 Heterogeneous nuclear ribonucleoprotein C1/C2, MeCP1, and SW... | ACCEPT | Summary: Retain nucleosomal DNA binding at the original contributes_to scope. Reason: Original human K562 LARC EMSA and restriction-accessibility experiments test a multi-subunit CHD4-containing assembly. Its contributes_to relation is preserved. Independent human CHD4 structure shows nucleosomal DNA engagement, but does not transform the original LARC assay into a purified motif-recognition assay. |
| GO:0032991 protein-containing complex | HDA PMID:16217013 Heterogeneous nuclear ribonucleoprotein C1/C2, MeCP1, and SW... | ACCEPT | Summary: CHD4 is a component of the purified human LARC assembly. Reason: PMID:16217013 purified a human K562 LCR-associated remodeling complex containing Mi2beta/CHD4, SWI/SNF components and hnRNP C1/C2. Size fractionation, coimmunoprecipitation and immunodepletion support a shared assembly (Results; Figure 3). Retain the broad complex term because this source identifies LARC, not simply NuRD. Sequence-specific MARE contact is assigned to hnRNP C1/C2, not intrinsic CHD4 recognition. Supporting Evidence: PMID:16217013 We call this protein complex LARC. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | MODIFY | Summary: Refine the broad complex membership to the supported NuRD assembly. Reason: The preserved mouse Q6PDQ2 donor currently carries the broad IDA assertion from PMID:19796622. Its full Results and Figure 6 identify CHD4 with HDAC1 and MBD3 in CDX2-associated NuRD preparations; the CHD4 identification is by mass spectrometry, not a CHD4-specific reverse-IP panel. Human ZIP-associated purification independently identifies Mi-2beta among NuRD components (PMID:19644445, Figure 4). These positive assembly data support NuRD as the useful target-specific refinement. The original Ensembl source and donor identifiers remain unchanged; the historical transfer event is not reconstructed. Proposed replacements: NuRD complex Supporting Evidence: GO_REF:0000107 file:human/CHD4/CHD4-source-evidence.json |
| GO:0032993 protein-DNA complex | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact stable DNA-containing complex assignment remains unresolved. Reason: Mouse Q6PDQ2 currently carries the same-term IDA assertion from PMID:21245044. The recovered full paper reports positive Mi-2 ChIP at Gata2 and CD4E1 control regions, but not the embryonic globin regions tested in Figure 2; the generic Mi-2 antibody experiments are not all uniquely assigned to CHD4. GO:0032993 requires DNA to be a constituent of the complex, rather than merely contacted by a protein assembly. These observations establish chromatin recruitment but do not resolve that membership requirement. Independent human CHD4βnucleosome contacts do not by themselves settle stable membership either. Preserve the original orthology assertion as undecided, without relabeling the proteinβDNA category as the protein-only NuRD assembly or denying the positive chromatin evidence. Supporting Evidence: GO_REF:0000107 file:human/CHD4/CHD4-source-evidence.json |
| GO:0042393 histone binding | IBA GO_REF:0000033 | ACCEPT | Summary: Histone recognition contributes to CHD4 nucleosome engagement. Reason: The PANTHER assertion is independently supported by the human CHD4 nucleosome structure, which positions PHD2 near the H3 tail and describes histone contacts of the ATPase region. This is substrate recognition, not histone methylation/deacetylation by CHD4. Historical node placement remains uninspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The curated ancestral source is retained; historical PAINT placement was not reconstructed. Independent target evidence supports biological applicability without donor-count or target-self-reference objections. Supporting Evidence: |
| GO:0042659 regulation of cell fate specification | NAS PMID:22560079 NuRD suppresses pluripotency gene expression to promote tran... | KEEP AS NON CORE | Summary: Retain the developmental consequence of NuRD-dependent transcriptional regulation. Reason: The original PMID:22560079 primarily perturbs mouse Mbd3/NuRD and measures Mi2beta occupancy at pluripotency targets, with lineage commitment and transcriptional heterogeneity outcomes. It is not a direct human CHD4-specific differentiation knockout. Retain the existing NAS association at conserved complex/organism scope; independent CHD4 remodeling provides a plausible performed transcriptional contribution without a new developmental process assertion. |
| GO:0042826 histone deacetylase binding | IPI PMID:27616479 De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remode... | ACCEPT | Summary: HDAC1 association is integral to CHD4-containing NuRD. Reason: Original human wild-type and patient-variant CHD4 co-IP retains HDAC1 in Fig.3A. Independent native and purified-protein studies establish the partner relationship. Binding an HDAC does not make CHD4 a histone deacetylase. |
| GO:0045892 negative regulation of DNA-templated transcription | NAS PMID:22560079 NuRD suppresses pluripotency gene expression to promote tran... | ACCEPT | Summary: Retain transcriptional repression as a core output of CHD4 remodeling. Reason: The original mouse Mbd3/NuRD study measures Mi2beta occupancy and transcriptional repression at pluripotency targets. Independent human CHD4 recruitment and erythroid rescue establish its regulatory contribution directly. Repression is context-dependent; other CHD4-containing assemblies can permit transcription. |
| GO:0045893 positive regulation of DNA-templated transcription | NAS PMID:19927129 NuRD mediates activating and repressive functions of GATA-1 ... | KEEP AS NON CORE | Summary: Retain context-dependent positive transcription regulation. Reason: The genuine fresh full PMID:19927129 reports mouse GATA1/FOG1βNuRD activation with Mi2beta promoter occupancy; the functional perturbations principally target FOG1/NuRD components rather than isolated CHD4. Independent human CHD4 expression studies and acute mouse CHD4 depletion support mixed transcriptional outcomes. The retained NAS term is not an autonomous activator MF or a claim that all targets are activated. |
| GO:0051963 regulation of synapse assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain nuclear transcriptional regulation of synaptic development. Reason: The literal rat E9PU01 donor traces to PMID:24991957. Rat and mouse neuronal experiments connect nuclear NuRD/Chd4 promoter decommissioning to bouton organization, ultrastructure and neurotransmission. This is a contextual regulatory process, not proof of CHD4 molecular activity within the synaptic compartment. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:22926524 RBB, a novel transcription repressor, represses the transcri... | KEEP AS NON CORE | Summary: Retain the curated Pol II transcription-factor association with RBB/NACC2. Reason: Q96BF6 is the human RBB/NACC2 transcriptional repressor. The authentic source abstract describes DNA-dependent recruitment of NuRD to HDM2/MDM2. Preserve the experimental CHD4 pair and its specific class, while acknowledging that the full CHD4-specific interaction series was not independently recovered. This individual recruiter is outside the core headline even though recruited corepression is central. |
| GO:0072553 terminal button organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain nuclear transcriptional regulation of synaptic development. Reason: The literal rat E9PU01 donor traces to PMID:24991957. Rat and mouse neuronal experiments connect nuclear NuRD/Chd4 promoter decommissioning to bouton organization, ultrastructure and neurotransmission. This is a contextual regulatory process, not proof of CHD4 molecular activity within the synaptic compartment. |
| GO:0090575 RNA polymerase II transcription regulator complex | IDA PMID:29795351 Activity-dependent neuroprotective protein recruits HP1 and ... | ACCEPT | Summary: Retain CHD4 in the ChAHP transcription-regulatory assembly. Reason: The original ADNP/CHD4/HP1 study establishes a chromatin-regulatory complex, with recombinant human interaction evidence and mouse ESC genomic experiments. ADNP supplies sequence-specific recruitment; CHD4 supplies ATP-dependent remodeling. The broad complex term does not imply that ChAHP is identical to NuRD. |
| GO:0090734 site of DNA damage | IDA PMID:25593309 Screen identifies bromodomain protein ZMYND8 in chromatin re... | ACCEPT | Summary: CHD4 is recruited to nuclear DNA-damage sites. Reason: PMID:25593309 Fig.4EβJ directly measures CHD4 damage accumulation and dependence on ZMYND8; Fig.6 studies local silencing and RAD51 loading. The rescue in the recruitment series is a ZMYND8 rescue, not an unreported CHD4 rescue. This location is part of the DNA-repair context of the nuclear remodeler. |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000120 | ACCEPT | Summary: Retain transcription-factor binding as a recruitment interface for CHD4. Reason: The mouse donor and ARBA identifiers remain exact. Independent human CHD4 interactions with DNA-binding regulators, including the human CHD4/mouse TBX5 construct series and human ADNP reconstitution, support this broad recruitment capability. CHD4 is not assigned its partners' DNA motifs. |
| GO:0140658 ATP-dependent chromatin remodeler activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATP-dependent chromatin remodeling is the defining CHD4 molecular activity. Reason: Purified human CHD4 hydrolyzes ATP and repositions nucleosomes; human nucleosome-bound structure identifies the motor-DNA and histone contacts. The full-length/tagged constructs are retained at their documented sequence scope rather than assigned to every current alternative product. No duplex-unwinding or HDAC activity is inferred from the protein name or complex membership. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The curated ancestral source is retained; historical PAINT placement was not reconstructed. Independent target evidence supports biological applicability without donor-count or target-self-reference objections. |
| GO:0140658 ATP-dependent chromatin remodeler activity | IDA PMID:28977666 CHD3 and CHD4 form distinct NuRD complexes with different ye... | ACCEPT | Summary: ATP-dependent chromatin remodeling is the defining CHD4 molecular activity. Reason: Purified human CHD4 hydrolyzes ATP and repositions nucleosomes; human nucleosome-bound structure identifies the motor-DNA and histone contacts. The full-length/tagged constructs are retained at their documented sequence scope rather than assigned to every current alternative product. No duplex-unwinding or HDAC activity is inferred from the protein name or complex membership. |
| GO:0150048 cerebellar granule cell to Purkinje cell synapse | IEA GO_REF:0000107 | UNDECIDED | Summary: The synaptic active-in assignment needs source-scope clarification. Reason: Current rat E9PU01 IDA and IMP donor rows already assert is_active_in GO:0150048 from PMID:24991957; the human orthology pipeline did not invent that relation. The actual paper establishes nuclear CHD4/NuRD promoter work and synaptic outcomes. Its GFP/synapsin/bassoon/PSD95 imaging does not localize CHD4 protein to the synapse. Because active-in requires a molecular activity in the component, the compartment assertion remains unresolved pending donor assay/convention clarification. An additional synaptic pool is not disproved. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:E9PU01 UNRESOLVED The donor already carries the same active-in CC relation; its assay/convention basis remains unresolved despite verified nuclear regulatory work. |
| GO:2000736 regulation of stem cell differentiation | NAS PMID:22560079 NuRD suppresses pluripotency gene expression to promote tran... | KEEP AS NON CORE | Summary: Retain the developmental consequence of NuRD-dependent transcriptional regulation. Reason: The original PMID:22560079 primarily perturbs mouse Mbd3/NuRD and measures Mi2beta occupancy at pluripotency targets, with lineage commitment and transcriptional heterogeneity outcomes. It is not a direct human CHD4-specific differentiation knockout. Retain the existing NAS association at conserved complex/organism scope; independent CHD4 remodeling provides a plausible performed transcriptional contribution without a new developmental process assertion. |
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Download this section (compressed HTML)Q: What assay or annotation convention supports CHD4 being active within the cerebellar granule-to-Purkinje synapse, beyond its demonstrated nuclear regulation of synaptic development?
Q: Which current CHD4 alternative products correspond to the recombinant constructs used in each remodeling, PAR-binding and recruitment study?
Q: What molecular step explains the distinct CHD3 and CHD4 effects on pericentrin at centrosomes, independently of longer-term transcriptional changes?
Q: Which original experiment links PMID:9804427 to the preserved mouse pericentrin partner, and where is the exact CHD4 target row in the NK membrane-proteome study?
Q: How do ADNP, NuRD and other recruiters tune CHD4 remodeling toward repression or transcriptional competence in different chromatin contexts?
Experiment: Use endogenous paralog-specific CHD4 tagging in cerebellar neurons with compartment-resolved imaging and local interaction measurements to distinguish nuclear regulation from a synaptic protein pool.
Experiment: Map the full recombinant sequences to current products and compare ATPase, remodeling and recruiter binding with matched substrates and tags.
Experiment: Separate rapid centrosomal CHD4 perturbation from slower gene-expression changes while measuring pericentrin exchange and centrosome composition.
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