CHD8 is a nuclear ATP-dependent chromatin remodeler that binds DNA and nucleosomes and changes nucleosome position and accessibility. Its interactions with transcriptional regulators, histones and chromatin-associated proteins support both repression and activation at different loci, including beta-catenin-responsive genes and Pol II/III transcriptional contexts. CHD8-dependent chromatin regulation also influences alternative RNA splicing and neurodevelopmental and enteric phenotypes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:25294932 CHD8 regulates neurodevelopmental pathways associated with a... | ACCEPT | Summary: Retain context-dependent repression of Pol II transcription. Reason: Human neural progenitor CHD8 suppression produces both increased and decreased transcripts, with CHD8 occupancy at a subset of affected loci. Repression is a core regulatory output, but the full transcriptome response is not equated with direct promoter binding. Supporting Evidence: |
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: Chromatin is the substrate and principal site of CHD8 activity. Reason: Human purified-protein remodeling and cellular occupancy support this active-in assertion. Retain the curated PTN002473914 propagation without claiming that its historical ancestral placement was reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. |
| GO:0002039 p53 binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain p53 association in the transcriptional stress-response context. Reason: The exact mouse Q09XV5 donor has p53-binding IPI evidence from PMID:19151705. That full source also reports endogenous human CHD8–p53 co-IP; recombinant direct-binding experiments primarily use mouse short CHD8. This supports the conserved relationship without equating mouse motorless CHD8S with either current human long product. Supporting Evidence: |
| GO:0002039 p53 binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain p53 association in the transcriptional stress-response context. Reason: The exact mouse Q09XV5 donor has p53-binding IPI evidence from PMID:19151705. That full source also reports endogenous human CHD8–p53 co-IP; recombinant direct-binding experiments primarily use mouse short CHD8. This supports the conserved relationship without equating mouse motorless CHD8S with either current human long product. Supporting Evidence: |
| GO:0003677 DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: DNA engagement is part of the CHD8 remodeling mechanism. Reason: Purified human CHD8 binds DNA in EMSA and remodels nucleosomes. The broad term does not assign sequence-specific transcription-factor recognition; the original IBA source is retained alongside independent direct biochemical support. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: DNA engagement is part of the CHD8 remodeling mechanism. Reason: Purified human CHD8 binds DNA in EMSA and remodels nucleosomes. The broad term does not assign sequence-specific transcription-factor recognition; the original IEA source is retained alongside independent direct biochemical support. |
| GO:0003677 DNA binding | IMP PMID:18378692 CHD8 is an ATP-dependent chromatin remodeling factor that re... | ACCEPT | Summary: DNA engagement is part of the CHD8 remodeling mechanism. Reason: Purified human CHD8 binds DNA in EMSA and remodels nucleosomes. The broad term does not assign sequence-specific transcription-factor recognition; the original IMP source is retained alongside independent direct biochemical support. |
| GO:0003678 DNA helicase activity | IEA GO_REF:0000104 | MODIFY | Summary: Replace inferred DNA helicase activity with the demonstrated chromatin-remodeling activity. Reason: GO:0003678 describes DNA strand unwinding. The measured human CHD8 reaction is ATP-dependent nucleosome repositioning and increased nucleosomal DNA accessibility. The SNF2 motor/domain name alone does not establish helicase strand separation. GO:0140658 captures the positive target evidence, without a universal claim that CHD8 could never unwind DNA under any condition. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniRule:UR000369261 UNRESOLVED Original rule identifier retained; historical rule execution not reconstructed. Target assays support the proposed activity/process scope rather than the original broader or different term. Proposed replacements: ATP-dependent chromatin remodeler activity |
| GO:0003682 chromatin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Retain chromatin binding as part of the nuclear remodeler function. Reason: Direct human DNA/nucleosome assays and chromatin occupancy support substrate engagement. The source propagation is preserved and independently corroborated, not reconstructed from a donor count. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. |
| GO:0003682 chromatin binding | IDA PMID:22083958 Histone H1 recruitment by CHD8 is essential for suppression ... | ACCEPT | Summary: Retain chromatin binding as part of the nuclear remodeler function. Reason: Direct human DNA/nucleosome assays and chromatin occupancy support substrate engagement. The original study includes human endogenous promoter occupancy, while much of its H1-bridging construct work uses mouse short CHD8; those assay scopes are kept separate. |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Retain chromatin binding as part of the nuclear remodeler function. Reason: Direct human DNA/nucleosome assays and chromatin occupancy support substrate engagement. The source propagation is preserved and independently corroborated, not reconstructed from a donor count. |
| GO:0005515 protein binding | IPI PMID:15960975 Physical association and coordinate function of the H3 K4 me... | MODIFY | Summary: Refine the demonstrated partner class. Reason: The original WDR5 purification detects CHD8 in bands 2 and 3 of Fig. 1B. Mixed subfractions do not alone prove a single intact MLL1 particle. Independent direct CHD8–WDR5 pull-down confirms the same partner. WDR5 is independently established as a transcriptional cofactor; GO:0001221 refines the binding partner class without assigning its cofactor function to CHD8 or requiring invariant MLL1 membership. Proposed replacements: transcription coregulator binding |
| GO:0005515 protein binding | IPI PMID:17938208 CHD8 associates with human Staf and contributes to efficient... | MODIFY | Summary: Refine the demonstrated partner class. Reason: Human endogenous reciprocal co-IP and hStaf/ZNF143 affinity purification establish association. ZNF143 supplies sequence-specific promoter recognition; recruitment direction and a purified binary interface are not inferred. GO:0140297 describes binding the verified DNA-binding transcription factor, not DNA binding by CHD8. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18378692 CHD8 is an ATP-dependent chromatin remodeling factor that re... | MODIFY | Summary: Refine the demonstrated partner class. Reason: Original recombinant CHD8 and GST-WDR5 pull-down supports direct association. The same CHD8 preparation lacks MLL proteins, so WDR5 binding is not treated as synonymous with invariant MLL1 membership. WDR5 is independently established as a transcriptional cofactor; GO:0001221 refines the binding partner class without assigning its cofactor function to CHD8 or requiring invariant MLL1 membership. Proposed replacements: transcription coregulator binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20085832 Regulation of HOXA2 gene expression by the ATP-dependent chr... | MODIFY | Summary: Refine the demonstrated partner class. Reason: Tagged Sf9 pairwise coexpression and affinity recovery supports CHD8–WDR5 association; four-protein WAR/CHD8 assembly and human HOXA2 chromatin experiments provide context. MLL1 is not required in that reconstitution. WDR5 is independently established as a transcriptional cofactor; GO:0001221 refines the binding partner class without assigning its cofactor function to CHD8 or requiring invariant MLL1 membership. Proposed replacements: transcription coregulator binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20085832 Regulation of HOXA2 gene expression by the ATP-dependent chr... | KEEP AS NON CORE | Summary: Retain the demonstrated association at its source-specific scope. Reason: Tagged Sf9 pairwise coexpression and affinity recovery support CHD8–RBBP5 association in the WAR assembly. RBBP5 is a transcriptional cofactor, but the literal GO:0001221 definition excludes cofactors that bind DNA directly. Independent human RBBP5 experiments in PMID:31544921 test purified full-length 2–538 protein and its CTD3 region by DNA fluorescence polarization, with lysine-mutant controls. This is measured DNA binding, not an inference from domain presence or absence. WDR5 histone-H3 contact is not DNA contact and therefore is not the same exclusion. Neither this DNA association nor the positive CHD8 pair establishes sequence-specific transcription-factor binding or CHD8 methyltransferase activity. Retain this supported association as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions; absence of a justified specific class does not call for deletion under that campaign instruction. |
| GO:0005515 protein binding | IPI PMID:20085832 Regulation of HOXA2 gene expression by the ATP-dependent chr... | KEEP AS NON CORE | Summary: Retain the demonstrated association at its source-specific scope. Reason: Original tagged Sf9 pairwise coexpression/affinity recovery supports CHD8–ASH2L association. Independent human ASH2L full-length and N-terminal-domain EMSA in PMID:21660059 demonstrates direct DNA binding; sequence selection did not establish strong motif specificity. The non-DNA-binding clause of GO:0001221 therefore is a poor literal fit, and a DNA-binding-transcription-factor class is not inferred from nonspecific contact. This does not transfer ASH2L properties or methyltransferase chemistry to CHD8. Retain this supported association as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions; absence of a justified specific class does not call for deletion under that campaign instruction. |
| GO:0005515 protein binding | IPI Q9HCK8-2 PMID:20453063 CHD8 interacts with CHD7, a protein which is mutated in CHAR... | MODIFY | Summary: Refine the demonstrated partner class. Reason: The actual source uses NP_065971.2 CHD8-2 fragments: residues 1789–1983 in Y2H and 1789–2302 in tagged co-IP, with overlapping BiFC constructs in HeLa cells. WT interactions are positive; some CHD7 mutants lose Y2H but retain co-IP. This is not a full-length pair assay. Independent purified human CHD7 ATP hydrolysis establishes the partner class in GO:0051117; binding does not imply activation of that ATPase. Proposed replacements: ATPase binding |
| GO:0005515 protein binding | IPI Q9HCK8-2 PMID:23285124 Identification and characterization of FAM124B as a novel co... | KEEP AS NON CORE | Summary: Retain the demonstrated association at its source-specific scope. Reason: Both full human FAM124B alternatives were tested with CHD8-2 residues 1789–2302 in co-IP and Y2H. The original Q9H5Z6-1 product is retained; FAM124B bait autoactivation was avoided by using it as prey. FAM124B's molecular activity remains unresolved, so no informative partner-class term can replace bare protein binding. Retain this supported association as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions; absence of a justified specific class does not call for deletion under that campaign instruction. Supporting Evidence: |
| GO:0005515 protein binding | IPI Q9HCK8-2 PMID:23285124 Identification and characterization of FAM124B as a novel co... | KEEP AS NON CORE | Summary: Retain the demonstrated association at its source-specific scope. Reason: Both full human FAM124B alternatives were tested with CHD8-2 residues 1789–2302 in co-IP and Y2H. The original Q9H5Z6-2 product is retained; no full-length CHD8 complex or product-exclusive function is claimed. FAM124B's molecular activity remains unresolved, so no informative partner-class term can replace bare protein binding. Retain this supported association as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions; absence of a justified specific class does not call for deletion under that campaign instruction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26816381 Transcription factors LRF and BCL11A independently repress e... | MODIFY | Summary: Refine the demonstrated partner class. Reason: Full main Results explicitly validates CHD8 association with LRF/ZBTB7A by immunoprecipitation after a human LRF-BTB Y2H screen (Fig. S12B). The exact supplementary construct panel was not independently inspected. LRF has sequence-specific DNA recognition; endogenous NuRD assays elsewhere in the paper are not all CHD8 assays. GO:0140297 describes binding the verified DNA-binding transcription factor, not DNA binding by CHD8. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26949739 Identification of Human Neuronal Protein Complexes Reveals B... | MODIFY | Summary: Refine the demonstrated partner class. Reason: Replicated endogenous human differentiated SH-SY5Y IP-MS and the source Fig. 5B validation identify CHD8–ACOT7 association. ACOT7 is an acyl-CoA hydrolase. This class refinement does not assign lipid metabolism to CHD8 or require a purified binary-contact claim. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36537238 CHD8 suppression impacts on histone H3 lysine 36 trimethylat... | KEEP AS NON CORE | Summary: Retain the demonstrated association at its source-specific scope. Reason: Human neural-progenitor nuclear IP-MS and co-IP validate HNRNPL association. DNA-disrupting treatments preserve association, whereas RNase partly reduces it. The association does not establish CHD8 RNA binding or an isolated CHD8-HNRNPL interface, and no more specific partner-class term is supported here. Retain this supported association as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions; absence of a justified specific class does not call for deletion under that campaign instruction. Supporting Evidence: |
| GO:0005524 ATP binding | IDA PMID:18378692 CHD8 is an ATP-dependent chromatin remodeling factor that re... | ACCEPT | Summary: ATP binding supports the CHD8 motor cycle. Reason: Purified human CHD8 ATP hydrolysis and ATP-dependent nucleosome repositioning establish nucleotide engagement. The source is retained independently of the more informative integrated motor term. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: ATP binding supports the CHD8 motor cycle. Reason: Purified human CHD8 ATP hydrolysis and ATP-dependent nucleosome repositioning establish nucleotide engagement. The source is retained independently of the more informative integrated motor term. |
| GO:0005634 nucleus | EXP PMID:36537238 CHD8 suppression impacts on histone H3 lysine 36 trimethylat... | ACCEPT | Summary: Retain the nucleus as a core compartment. Reason: Human neural-progenitor fractionation and nuclear IP provide direct endogenous evidence. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the nucleus as a core compartment. Reason: The active-in PAINT relation is supported by performed nuclear chromatin work; ancestral placement remains uninspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. |
| GO:0005634 nucleus | IDA PMID:18378692 CHD8 is an ATP-dependent chromatin remodeling factor that re... | ACCEPT | Summary: Retain the nucleus as a core compartment. Reason: Original endogenous human nuclear purification and promoter occupancy support this location. |
| GO:0005634 nucleus | IDA PMID:20453063 CHD8 interacts with CHD7, a protein which is mutated in CHAR... | ACCEPT | Summary: Retain the nucleus as a core compartment. Reason: Original HeLa BiFC uses CHD8-2 C-terminal fragments and reports nuclear signal; independent endogenous studies support whole-gene nuclear location. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the nucleus as a core compartment. Reason: The original mouse and sequence/rule sources are corroborated by direct human nuclear evidence. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Retain nucleoplasmic localization. Reason: HPA XML identifies CHD8 nucleoplasmic staining. The inspected A431/HPA052186 and RT4/HPA076133 images show nuclear green signal with DNA and microtubule reference channels. Other reported HPA compartments are not taken as new mechanistic claims. Supporting Evidence: GO_REF:0000052 |
| GO:0005654 nucleoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: Retain the electronically inferred nucleoplasmic location. Reason: The original ARBA source remains unchanged and is corroborated by human nuclear fractionation, promoter occupancy and HPA imaging. This is a location assertion, not a claim that every CHD8 molecule is always nuclear. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5368580 | ACCEPT | Summary: Retain the compartment of the represented CHD8 reaction or assembly. Reason: The official event 'CHD8 binds beta-catenin to negatively regulate WNT-dependent gene expression' places the represented target in the nucleoplasm. Literal CHD8 entity R-HSA-3221598 maps to Q9HCK8 residues 1–2581; candidate-set membership is distinguished from inferred alternative enzymes. No other component's catalytic activity is assigned to CHD8. Supporting Evidence: Reactome:R-HSA-5368580 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9944087 | ACCEPT | Summary: Retain the compartment of the represented CHD8 reaction or assembly. Reason: The official event 'CHD6-9-dependent ATP hydrolysis' places the represented target in the nucleoplasm. Literal CHD8 entity R-HSA-3221598 maps to Q9HCK8 residues 1–2581; candidate-set membership is distinguished from inferred alternative enzymes. No other component's catalytic activity is assigned to CHD8. Supporting Evidence: Reactome:R-HSA-9944087 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9944419 | ACCEPT | Summary: Retain the compartment of the represented CHD8 reaction or assembly. Reason: The official event 'CHD8 and CHD7 bind CTCF' places the represented target in the nucleoplasm. Literal CHD8 entity R-HSA-3221598 maps to Q9HCK8 residues 1–2581; candidate-set membership is distinguished from inferred alternative enzymes. No other component's catalytic activity is assigned to CHD8. Supporting Evidence: Reactome:R-HSA-9944419 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9944450 | ACCEPT | Summary: Retain the compartment of the represented CHD8 reaction or assembly. Reason: The official event 'CHD7 and CHD8 bind FAM124B' places the represented target in the nucleoplasm. Literal CHD8 entity R-HSA-3221598 maps to Q9HCK8 residues 1–2581; candidate-set membership is distinguished from inferred alternative enzymes. No other component's catalytic activity is assigned to CHD8. Supporting Evidence: Reactome:R-HSA-9944450 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9944456 | ACCEPT | Summary: Retain the compartment of the represented CHD8 reaction or assembly. Reason: The official event 'CHD8 binds WDR5' places the represented target in the nucleoplasm. Literal CHD8 entity R-HSA-3221598 maps to Q9HCK8 residues 1–2581; candidate-set membership is distinguished from inferred alternative enzymes. No other component's catalytic activity is assigned to CHD8. Supporting Evidence: Reactome:R-HSA-9944456 |
| GO:0006338 chromatin remodeling | IBA GO_REF:0000033 | ACCEPT | Summary: Retain chromatin remodeling as CHD8 performed core work. Reason: Human purified CHD8 changes nucleosome position/accessibility in an ATP-dependent reaction. CHD8 supplies the motor activity itself; this is not merely a downstream perturbation phenotype. Original evidence codes and source objects remain unchanged. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. |
| GO:0006338 chromatin remodeling | IEA GO_REF:0000120 | ACCEPT | Summary: Retain chromatin remodeling as CHD8 performed core work. Reason: Human purified CHD8 changes nucleosome position/accessibility in an ATP-dependent reaction. CHD8 supplies the motor activity itself; this is not merely a downstream perturbation phenotype. Original evidence codes and source objects remain unchanged. |
| GO:0006338 chromatin remodeling | IMP PMID:18378692 CHD8 is an ATP-dependent chromatin remodeling factor that re... | ACCEPT | Summary: Retain chromatin remodeling as CHD8 performed core work. Reason: Human purified CHD8 changes nucleosome position/accessibility in an ATP-dependent reaction. CHD8 supplies the motor activity itself; this is not merely a downstream perturbation phenotype. Original evidence codes and source objects remain unchanged. |
| GO:0006397 mRNA processing | IMP PMID:36537238 CHD8 suppression impacts on histone H3 lysine 36 trimethylat... | MODIFY | Summary: Refine the observed processing effect to regulation of RNA splicing. Reason: Three partial CHD8-suppression human neural-progenitor lines show differential alternative splicing, with ITSN1 isoform-PCR validation. CHD8 chromatin association and HNRNPL interaction provide performed regulatory context. GO:0043484 captures modulation of splicing more precisely than broad mRNA processing. H3K36me3 and HNRNPL provide a mechanistic model; the study does not establish CHD8 splicease or histone-methyltransferase chemistry. Proposed replacements: regulation of RNA splicing Supporting Evidence: PMID:36537238 altered splicing patterns following CHD8 suppression |
| GO:0007420 brain development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the developmental consequence of CHD8-dependent regulation. Reason: The source combines human disruptive variants with zebrafish perturbations showing brain overgrowth. This supports conserved neurodevelopmental involvement, while human cellular chromatin studies establish the underlying molecular role. Neither every clinical feature nor a direct neural-growth catalytic activity is inferred. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002898830 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. |
| GO:0007420 brain development | IMP PMID:24998929 Disruptive CHD8 mutations define a subtype of autism early i... | KEEP AS NON CORE | Summary: Retain the developmental consequence of CHD8-dependent regulation. Reason: The source combines human disruptive variants with zebrafish perturbations showing brain overgrowth. This supports conserved neurodevelopmental involvement, while human cellular chromatin studies establish the underlying molecular role. Neither every clinical feature nor a direct neural-growth catalytic activity is inferred. |
| GO:0008013 beta-catenin binding | IDA PMID:18378692 CHD8 is an ATP-dependent chromatin remodeling factor that re... | ACCEPT | Summary: Retain beta-catenin binding in the transcription-regulatory mechanism. Reason: Human CHD8 associates with beta-catenin and is recruited to beta-catenin-responsive chromatin. Purified full-length human CHD8 and GST-beta-catenin provide direct binding evidence in PMID:18378692. Supporting Evidence: PMID:18378692 full-length CHD8 interacts directly with beta-catenin |
| GO:0008013 beta-catenin binding | IDA PMID:22083958 Histone H1 recruitment by CHD8 is essential for suppression ... | ACCEPT | Summary: Retain beta-catenin binding in the transcription-regulatory mechanism. Reason: Human CHD8 associates with beta-catenin and is recruited to beta-catenin-responsive chromatin. The original paper includes endogenous human co-IP, but its detailed H1-bridging experiments use mouse short CHD8 constructs; those are not assigned to both human long products. |
| GO:0008013 beta-catenin binding | IEA GO_REF:0000104 | ACCEPT | Summary: Retain beta-catenin binding in the transcription-regulatory mechanism. Reason: Human CHD8 associates with beta-catenin and is recruited to beta-catenin-responsive chromatin. Purified full-length human CHD8 and GST-beta-catenin provide direct binding evidence in PMID:18378692. |
| GO:0008094 ATP-dependent activity, acting on DNA | IEA GO_REF:0000104 | MODIFY | Summary: Specify the ATP-dependent chromatin-remodeling reaction. Reason: GO:0008094 is broad. Purified human CHD8 provides ATP-dependent nucleosome repositioning and accessibility changes, captured by GO:0140658. This overlaps existing source assertions but refines the original electronic assertion without adding a NEW row. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniRule:UR000369261 UNRESOLVED Original rule identifier retained; historical rule execution not reconstructed. Target assays support the proposed activity/process scope rather than the original broader or different term. Proposed replacements: ATP-dependent chromatin remodeler activity |
| GO:0016887 ATP hydrolysis activity | EXP PMID:18378692 CHD8 is an ATP-dependent chromatin remodeling factor that re... | ACCEPT | Summary: Retain ATP hydrolysis as the motor energy reaction. Reason: Direct purified human CHD8 ATPase measurements and ATP-dependent nucleosome remodeling support the original assertion. Retaining hydrolysis alongside the integrated remodeler activity does not assign a separate unrelated enzyme function. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:28533432 The ATP-dependent chromatin remodeling enzymes CHD6, CHD7, a... | ACCEPT | Summary: Retain ATP hydrolysis as the motor energy reaction. Reason: Direct purified human CHD8 ATPase measurements and ATP-dependent nucleosome remodeling support the original assertion. Retaining hydrolysis alongside the integrated remodeler activity does not assign a separate unrelated enzyme function. |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: Retain ATP hydrolysis as the motor energy reaction. Reason: Direct purified human CHD8 ATPase measurements and ATP-dependent nucleosome remodeling support the original assertion. Retaining hydrolysis alongside the integrated remodeler activity does not assign a separate unrelated enzyme function. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: Retain ATP hydrolysis as the motor energy reaction. Reason: Direct purified human CHD8 ATPase measurements and ATP-dependent nucleosome remodeling support the original assertion. Retaining hydrolysis alongside the integrated remodeler activity does not assign a separate unrelated enzyme function. |
| GO:0030178 negative regulation of Wnt signaling pathway | IEA GO_REF:0000104 | MODIFY | Summary: Specify the canonical beta-catenin branch of Wnt regulation. Reason: The demonstrated target-promoter and beta-catenin/H1 mechanism concerns canonical Wnt output. GO:0090090 describes this positive source scope more precisely than the broad Wnt term; no claim is made about every noncanonical Wnt pathway. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniRule:UR000369261 UNRESOLVED Original rule identifier retained; historical rule execution not reconstructed. Target assays support the proposed activity/process scope rather than the original broader or different term. Proposed replacements: negative regulation of canonical Wnt signaling pathway |
| GO:0032991 protein-containing complex | IDA PMID:18378692 CHD8 is an ATP-dependent chromatin remodeling factor that re... | KEEP AS NON CORE | Summary: Retain the broad protein-complex context as non-core. Reason: Native preparations and partner reconstitution establish physical assemblies. This broad root complex term is retained as contextual localization rather than a defining core identity. It is not equated with an invariant MLL1 complex or one assembly containing every recovered partner; the more specific MLL1 assertions retain their own source-dependent qualifications. |
| GO:0042393 histone binding | IBA GO_REF:0000033 | ACCEPT | Summary: Histone recognition is part of CHD8 chromatin engagement. Reason: Human CHD8-containing fractions preferentially recover methylated H3 peptides, and mouse short-form studies directly test H1 binding. These distinct assays support the broad histone-binding assertion without assigning every contact or mouse short-form mechanism to both human products. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. |
| GO:0042393 histone binding | IEA GO_REF:0000120 | ACCEPT | Summary: Histone recognition is part of CHD8 chromatin engagement. Reason: Human CHD8-containing fractions preferentially recover methylated H3 peptides, and mouse short-form studies directly test H1 binding. These distinct assays support the broad histone-binding assertion without assigning every contact or mouse short-form mechanism to both human products. |
| GO:0042393 histone binding | ISS GO_REF:0000024 | ACCEPT | Summary: Histone recognition is part of CHD8 chromatin engagement. Reason: Human CHD8-containing fractions preferentially recover methylated H3 peptides, and mouse short-form studies directly test H1 binding. These distinct assays support the broad histone-binding assertion without assigning every contact or mouse short-form mechanism to both human products. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain suppression of p53-dependent apoptosis in the tested context. Reason: The exact mouse donor is supported by PMID:19151705; the same full source includes human-cell CHD8 depletion and p53-codepletion rescue. Detailed H1 recruitment uses mouse short CHD8. This is context-dependent transcriptional protection, not a generic antiapoptotic enzyme activity or an all-product property. Supporting Evidence: |
| GO:0045892 negative regulation of DNA-templated transcription | IBA GO_REF:0000033 | ACCEPT | Summary: Retain negative transcriptional regulation as a core outcome. Reason: CHD8 promoter occupancy, beta-catenin association and depletion-dependent target activation establish performed repression. Other targets are positively regulated, so the retained term does not mean all CHD8-responsive genes are repressed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002898830 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000120 | ACCEPT | Summary: Retain negative transcriptional regulation as a core outcome. Reason: CHD8 promoter occupancy, beta-catenin association and depletion-dependent target activation establish performed repression. Other targets are positively regulated, so the retained term does not mean all CHD8-responsive genes are repressed. |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:18378692 CHD8 is an ATP-dependent chromatin remodeling factor that re... | ACCEPT | Summary: Retain negative transcriptional regulation as a core outcome. Reason: CHD8 promoter occupancy, beta-catenin association and depletion-dependent target activation establish performed repression. Other targets are positively regulated, so the retained term does not mean all CHD8-responsive genes are repressed. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:17938208 CHD8 associates with human Staf and contributes to efficient... | ACCEPT | Summary: Retain context-dependent positive transcriptional regulation. Reason: The original ZNF143/hStaf study measures CHD8 occupancy and CHD8-depletion effects on U6 reporter transcription and IRF3 expression. This supports positive regulation in defined chromatin contexts rather than a universal coactivator function. This existing parent overlaps the separately retained Pol II and Pol III children; it is preserved as source provenance rather than proposed as additional process coverage. The structured core uses the more specific contexts. Supporting Evidence: |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000104 | ACCEPT | Summary: Retain context-dependent positive transcriptional regulation. Reason: The original ZNF143/hStaf study measures CHD8 occupancy and CHD8-depletion effects on U6 reporter transcription and IRF3 expression. This supports positive regulation in defined chromatin contexts rather than a universal coactivator function. This existing parent overlaps the separately retained Pol II and Pol III children; it is preserved as source provenance rather than proposed as additional process coverage. The structured core uses the more specific contexts. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:17938208 CHD8 associates with human Staf and contributes to efficient... | ACCEPT | Summary: Retain context-dependent positive transcriptional regulation. Reason: The original ZNF143/hStaf study measures CHD8 occupancy and CHD8-depletion effects on U6 reporter transcription and IRF3 expression. IRF3 is the Pol II target; U6 reporter effects are kept separate. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:25294932 CHD8 regulates neurodevelopmental pathways associated with a... | ACCEPT | Summary: Retain context-dependent positive transcriptional regulation. Reason: Human neural progenitor suppression reduces expression of a subset of genes, with direct CHD8 occupancy at some targets and indirect effects at others. This supports positive regulation in defined chromatin contexts rather than a universal coactivator function. Supporting Evidence: |
| GO:0045945 positive regulation of transcription by RNA polymerase III | IMP PMID:17938208 CHD8 associates with human Staf and contributes to efficient... | ACCEPT | Summary: Retain context-dependent positive transcriptional regulation. Reason: The original ZNF143/hStaf study measures CHD8 occupancy and CHD8-depletion effects on U6 reporter transcription and IRF3 expression. The unstable U6 reporter supplies a Pol III-specific readout; this is not inferred from the Pol II IRF3 assay. Supporting Evidence: |
| GO:0048565 digestive tract development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain digestive-tract developmental involvement at organismal scope. Reason: The original human syndrome and zebrafish experiments link CHD8 loss to reduced enteric neuronal colonization and delayed transit. Chromatin-regulatory work offers the mechanistic context; no direct digestive enzyme or intestinal transport activity is assigned. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002898830 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. Supporting Evidence: |
| GO:0048565 digestive tract development | IMP PMID:24998929 Disruptive CHD8 mutations define a subtype of autism early i... | KEEP AS NON CORE | Summary: Retain digestive-tract developmental involvement at organismal scope. Reason: The original human syndrome and zebrafish experiments link CHD8 loss to reduced enteric neuronal colonization and delayed transit. Chromatin-regulatory work offers the mechanistic context; no direct digestive enzyme or intestinal transport activity is assigned. Supporting Evidence: |
| GO:0071339 MLL1 complex | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain context-dependent MLL1-complex association. Reason: Original WDR5 purification detects CHD8 with MLL-containing fractions, whereas the 2008 reverse CHD8 preparation lacks MLL. The 2026 study independently reports reciprocal CHD8–KMT2A co-IP in human HTR8 nuclear extracts; hTSC chromatin profiling is a separate assay. These observations support contextual membership without invariant stoichiometry, a purified intact particle or established recruitment order. CHD8 is not assigned methyltransferase chemistry. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002898830 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. |
| GO:0071339 MLL1 complex | IDA PMID:15960975 Physical association and coordinate function of the H3 K4 me... | KEEP AS NON CORE | Summary: Retain context-dependent MLL1-complex association. Reason: Original WDR5 purification detects CHD8 with MLL-containing fractions, whereas the 2008 reverse CHD8 preparation lacks MLL. The 2026 study independently reports reciprocal CHD8–KMT2A co-IP in human HTR8 nuclear extracts; hTSC chromatin profiling is a separate assay. These observations support contextual membership without invariant stoichiometry, a purified intact particle or established recruitment order. CHD8 is not assigned methyltransferase chemistry. |
| GO:0071339 MLL1 complex | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Retain context-dependent MLL1-complex association. Reason: Original WDR5 purification detects CHD8 with MLL-containing fractions, whereas the 2008 reverse CHD8 preparation lacks MLL. The 2026 study independently reports reciprocal CHD8–KMT2A co-IP in human HTR8 nuclear extracts; hTSC chromatin profiling is a separate assay. These observations support contextual membership without invariant stoichiometry, a purified intact particle or established recruitment order. CHD8 is not assigned methyltransferase chemistry. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Retain regulation of canonical Wnt transcriptional output. Reason: CHD8 beta-catenin association, target-promoter occupancy and transcriptional repression supply performed regulation of canonical Wnt output. This is a nuclear regulatory mechanism, not ligand/receptor chemistry. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002898830 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IDA PMID:18378692 CHD8 is an ATP-dependent chromatin remodeling factor that re... | ACCEPT | Summary: Retain regulation of canonical Wnt transcriptional output. Reason: CHD8 beta-catenin association, target-promoter occupancy and transcriptional repression supply performed regulation of canonical Wnt output. This is a nuclear regulatory mechanism, not ligand/receptor chemistry. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IDA PMID:22083958 Histone H1 recruitment by CHD8 is essential for suppression ... | ACCEPT | Summary: Retain regulation of canonical Wnt transcriptional output. Reason: CHD8 beta-catenin association, target-promoter occupancy and transcriptional repression supply performed regulation of canonical Wnt output. The original acts_upstream_of_or_within qualifier remains exact; the detailed H1-bridging constructs are mouse short CHD8, alongside endogenous human association/occupancy evidence. |
| GO:0140002 histone H3K4me3 reader activity | IDA PMID:17938208 CHD8 associates with human Staf and contributes to efficient... | KEEP AS NON CORE | Summary: Retain the positive methylated-H3 assay as non-core recognition context. Reason: The primary peptide assay preferentially recovers CHD8 with H3K4 di- and trimethylated peptides from a partially purified GST-hStaf fraction containing other proteins. The RNase control excludes a required RNA bridge under that condition but does not exclude a protein intermediary. This is positive evidence supporting the curated recognition assertion, not grounds to reject it for lack of a purified binary experiment. Non-core prominence reflects the source-specific fraction assay and unresolved autonomous recognition mechanism, while direct human ATP-dependent nucleosome remodeling remains the defining core. No isolated CHD8 chromodomain measurement is claimed. Supporting Evidence: PMID:17938208 CHD8 interacts preferentially with histone H3 di- and trimethylated on lysine 4 |
| GO:0140658 ATP-dependent chromatin remodeler activity | IBA GO_REF:0000033 | ACCEPT | Summary: Retain ATP-dependent chromatin remodeling as the principal molecular activity. Reason: Direct human purified-protein studies measure ATP-dependent nucleosome repositioning and accessibility. This is the integrated motor function; histone recognition, DNA/ATP binding and transcriptional outcomes are synthesized in the same core. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED Authenticated curated ancestral source retained. Historical PAINT tree/node placement was not independently reconstructed; target experiments corroborate biological applicability, not the precise ancestral reconstruction. Target self-evidence is legitimate. |
| GO:0140658 ATP-dependent chromatin remodeler activity | IDA PMID:18378692 CHD8 is an ATP-dependent chromatin remodeling factor that re... | ACCEPT | Summary: Retain ATP-dependent chromatin remodeling as the principal molecular activity. Reason: Direct human purified-protein studies measure ATP-dependent nucleosome repositioning and accessibility. This is the integrated motor function; histone recognition, DNA/ATP binding and transcriptional outcomes are synthesized in the same core. |
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Download this section (compressed HTML)Q: Which CHD8 product and protein interfaces account for H3K4 methyl-peptide recognition in a fully defined preparation, and how is this recognition coupled to remodeling?
Q: Under which human cell states does CHD8 assemble with intact KMT2A/MLL1 complexes, and what is the recruitment order relative to separate WDR5–ASH2L–RBBP5 assemblies?
Q: Which CHD8 chromatin and HNRNPL contacts causally alter alternative splicing, and can those effects be separated from transcription or H3K36me3 changes?
Q: How do the two current human long products compare functionally, and which mouse short-form p53/H1 mechanisms extend to each human product?
Experiment: Compare sequence-verified human products and reader-region mutants on matched modified/unmodified nucleosomes, measuring binding, ATPase and repositioning separately with protein-complex composition controls.
Hypothesis: Defined human CHD8 histone recognition influences nucleosome remodeling.
Experiment: Use reciprocal endogenous purification with quantitative composition and orthogonal size separation in matched human cell states, with WDR5/WAR controls and recruitment-time-course perturbations.
Hypothesis: CHD8 association with KMT2A complexes depends on cell state and is distinct from WAR-only assemblies.
Experiment: Separate interaction disruption from CHD8 abundance and motor activity in neural progenitors; measure nascent transcription, H3K36me3 and validated isoform ratios in the same rescue series.
Hypothesis: Specific CHD8–HNRNPL contacts contribute to splicing regulation.
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