CHD1

Summary: CHD1 localizes to the nucleus where it executes all known functions (transcription elongation, nucleosome organization, DNA repair). IBA evidence from phylogenetically conserved orthologs confirms nuclear localization across eukaryotes.

Reason: Nuclear localization is fundamental to CHD1's core functions. IBA annotation is well-supported by ortholog alignment and multiple experimental studies demonstrating CHD1 nuclear accumulation.

Summary: CHD1 contains SANT and SLIDE domains with intrinsic histone-binding capacity. However, biochemical studies show CHD1 makes minimal direct contacts with histone proteins during nucleosome remodeling, relying predominantly on DNA interactions. IBA annotation reflects ortholog conservation but oversimplifies the actual mechanism.

Reason: While histone binding capacity exists structurally, CHD1's primary nucleosome engagement mechanism relies on DNA binding through its SANT/SLIDE domains rather than histone contacts. This is a secondary capability, not the primary functional mode. Better core terms available (chromatin binding, DNA binding).

Summary: This is the defining molecular function of CHD1. CHD1 catalyzes ATP-dependent nucleosome repositioning and spacing through a ratcheting mechanism of its ATPase domain lobes. Cryo-EM structures confirm ATP-dependent conformational changes drive nucleosome translocation.

Reason: Core catalytic function. IBA annotation is fully justified by extensive biochemical and structural evidence. CHD1 is the paradigmatic ATP-dependent chromatin remodeler in yeast.

Summary: CHD1 directly engages chromatin to reposition nucleosomes. Located in chromatin on actively transcribed genes and at DSB sites. IBA annotation appropriately reflects chromatin association.

Reason: CHD1 acts directly on chromatin structures as a nucleosome remodeling enzyme. This is a core cellular component context for all its functions.

Summary: CHD1 is a primary nucleosome-spacing remodeler that generates and maintains regular nucleosomal arrays with ~159 bp spacing. IBA evidence from phylogenetically conserved orthologs strongly supports this annotation.

Reason: Core biological process function. CHD1 directly organizes nucleosome spacing genome-wide through ATP-dependent sliding and positioning.

Summary: CHD1 contains SNF2-related helicase domain with conserved ATPase catalytic motifs. ATP hydrolysis energizes DNA translocation and nucleosome repositioning. Both IBA and IDA evidence confirm this molecular function.

Reason: Core enzymatic activity. ATP hydrolysis is mechanistically coupled to nucleosome repositioning and spacing function.

Summary: CHD1 contains SANT and SLIDE DNA-binding domains that engage extranucleosomal DNA during nucleosome remodeling. IDA evidence confirms direct DNA engagement at multiple sites.

Reason: Core molecular function. DNA binding is essential for directionality and mechanism of nucleosome sliding. SANT/SLIDE domains specifically recognize and bind linker DNA.

Summary: CHD1 binds to chromatin and nucleosomes as its primary substrate. This is distinct from DNA binding - chromatin binding refers to binding the intact nucleosomal structure.

Reason: Core substrate interaction. CHD1 recognizes and binds to nucleosomal chromatin as its primary functional substrate for remodeling.

Summary: CHD1 is a component of the SAGA and SLIK histone acetyltransferase complexes (experimentally confirmed in IDA annotations below). IEA annotation based on ARBA mapping is correct but lacks mechanistic specificity.

Reason: CHD1 functions as a subunit of both SAGA and SLIK complexes. While IEA, this is supported by IDA evidence and literature.

Summary: CHD1 contains SNF2-related ATPase domain with ATP-binding motifs. This IEA annotation from UniProtKB keyword mapping correctly identifies nucleotide binding capability based on sequence homology to helicase family.

Reason: CHD1 binds ATP as substrate for catalytic activity. This is a well-established molecular function directly linked to IBA-supported ATP hydrolysis activity.

Summary: Redundant with IBA GO:0003677 DNA binding annotation above. IEA annotation from UniProtKB keyword mapping correctly identifies DNA binding based on SANT/SLIDE domains.

Reason: This is a duplicate of the IBA annotation (line 8 in GOA). Both are correct and represent convergent evidence. DNA binding is supported by IBA (ortholog comparison) and IEA (keyword mapping).

Summary: CHD1 contains conserved ATP-binding motifs (motifs I-VII) within its SNF2-related ATPase domain. IEA annotation from InterPro mapping correctly identifies ATP-binding capability.

Reason: Core molecular function. ATP binding is essential for catalytic activity and is clearly supported by domain structure and biochemical evidence.

Summary: Redundant with IBA GO:0005634 nucleus annotation (line 1). IEA annotation from UniProtKB subcellular location vocabulary correctly identifies nuclear localization. This represents convergent evidence sources.

Reason: This is a duplicate of the IBA annotation. Both correctly identify nuclear localization using different evidence approaches (phylogenetic vs. keyword mapping).

Summary: CHD1 organizes chromatin through nucleosome positioning and spacing. IEA annotation from UniProtKB keyword mapping (KW-0156) correctly maps "chromatin remodeling" activity to broader GO:0006325 chromatin organization process.

Reason: Core biological process. CHD1's nucleosome remodeling activity directly contributes to chromatin organization. IEA is appropriately general; more specific process terms (nucleosome organization) are captured in other annotations.

Summary: CHD1 functions in transcription elongation by maintaining nucleosome positioning during transcription. IEA annotation from UniProtKB keyword mapping (KW-0804) appropriately maps CHD1 to transcription process.

Reason: CHD1 works in transcription elongation context and is recruited by RNA Pol II-associated elongation factors. This IEA annotation correctly places CHD1 in transcription-related processes.

Summary: CHD1 is specifically required for RNA Pol II transcription elongation. IEA annotation from ARBA machine learning model correctly identifies CHD1's role in Pol II transcription.

Reason: CHD1 is directly recruited by Paf1 complex components associated with RNA Pol II and functions in Pol II-dependent transcription.

Summary: CHD1 regulates gene expression through chromatin remodeling that affects nucleosome positioning and transcription accessibility. IEA annotation from ARBA appropriately captures CHD1's broad role in gene regulation.

Reason: CHD1 regulates transcription elongation and transcription start site selection through nucleosome positioning. This appropriately general term complements more specific process terms.

Summary: CHD1 contains helicase domain with ATPase activity (hydrolysis of ATP). IEA annotation from UniProtKB keyword mapping (KW-0378) correctly identifies hydrolase function based on domain structure.

Reason: ATP hydrolysis is a hydrolase reaction. This is appropriately general parent term for ATP hydrolysis activity. Both specific (ATP hydrolysis) and general (hydrolase) terms are correctly used.

Summary: Redundant with IBA GO:0016887 ATP hydrolysis activity (line 5). IEA annotation from RHEA pathway mapping confirms ATP hydrolysis reaction. This represents convergent evidence sources.

Reason: This is a duplicate of the IBA annotation. Multiple evidence sources (IBA, IEA via RHEA) confirm ATP hydrolysis as core function.

Summary: Redundant with IBA GO:0034728 nucleosome organization (line 4). IEA annotation from ARBA machine learning independently confirms CHD1's role in nucleosome organization.

Reason: This is a duplicate of the IBA annotation. Multiple independent evidence sources (IBA, IEA/ARBA) strongly support nucleosome organization function.

Summary: Redundant with IBA GO:0140658 ATP-dependent chromatin remodeler activity (line 3). IEA annotation from ARBA machine learning independently confirms this core molecular function.

Reason: This is a duplicate of the IBA annotation. Multiple evidence sources converge on this core function.

Summary: CHD1 binds multiple protein partners in transcription elongation complexes (Spt5, Spt16, Pob3, Rtf1). IPI annotation documents protein interaction evidence from co-immunoprecipitation. However, "protein binding" is vague and non-informative.

Reason: While CHD1 clearly binds proteins, the generic term "protein binding" (GO:0005515) provides minimal functional information. Better to use specific interaction terms (chromatin binding, DNA binding) that describe actual catalytic/functional consequences. Multiple IPI annotations with same GO ID suggest evidence consolidation to specific binding type terms would be preferable.

Summary: Additional IPI evidence for CHD1 protein interactions from high-definition macromolecular composition studies. Same non-informative generic term as preceding annotation.

Reason: Generic protein binding term. While evidence is valid (high-throughput proteomics), this doesn't add functional insight beyond that already captured in more specific binding terms.

Summary: IPI evidence for protein interactions from proteome survey of yeast cell machinery. Same generic binding term.

Reason: Generic protein binding term from proteome-wide study. Specific binding partners and functional consequences already captured in transcription elongation and nucleosome organization annotations.

Summary: IPI evidence for protein complex interactions from global landscape of protein complexes in yeast. Generic binding term.

Reason: Generic protein binding annotation from large-scale protein complex study. Redundant with other protein binding IPI annotations.

Summary: IPI evidence from chaperone-protein interactions atlas. Generic binding term.

Reason: Generic protein binding from chaperone interaction study. Consistent evidence pattern but non-specific term.

Summary: IPI evidence from global protein kinase and phosphatase interaction network. Generic binding term.

Reason: Generic protein binding from kinase/phosphatase study. Non-informative generic term despite valid evidence.

Summary: IPI evidence from chromatin-associated interactome study. Generic binding term.

Reason: Generic protein binding from chromatin interactome. Multiple IPI annotations with same generic term should be consolidated to informative binding types.

Summary: IPI evidence from recent social and structural architecture of yeast protein interactome study. Generic binding term.

Reason: Generic protein binding from latest interactome study. Multiple redundant IPI annotations should prioritize specific binding interactions over generic protein binding.

Summary: CHD1's defining nucleosome spacing activity is documented through genetic interaction with Snf2-related nucleosome-spacing enzymes. IGI evidence documents functional specification of CHD1's spacing role.

Reason: Core molecular function. CHD1 is a primary nucleosome-spacing enzyme with specific activity in generating regular nucleosomal arrays. IGI evidence with related spacing remodelers appropriately characterizes this function.

Summary: IMP evidence from direct experimental manipulation demonstrates CHD1 sets nucleosome spacing in vivo. CHD1 and ISW1 compete to establish different spacing patterns.

Reason: Core molecular function directly demonstrated through experimental perturbation. IMP evidence is among strongest. CHD1 is a paradigmatic nucleosome-spacing remodeler.

Summary: IGI evidence from same study documenting genetic interaction between CHD1 and ISW1 in nucleosome spacing. Redundant with IMP annotation from same paper.

Reason: This is a duplicate of preceding annotation (same GO term, same PMID, different evidence codes). Both IGI and IMP evidence from same study demonstrate competitive nucleosome spacing function.

Summary: Redundant with IBA and IEA nucleus annotations (lines 1 and 13). NAS evidence from literature statement about nuclear localization represents weakest evidence form for well-established function.

Reason: This is a redundant annotation with two stronger evidence sources (IBA, IEA) already present. NAS is narrative assertion but conclusion is well-supported.

Summary: CHD1 functions in transcription elongation and transcriptional regulation through nucleosome repositioning. NAS evidence from literature narrative appropriately captures CHD1's regulatory role in transcription.

Reason: CHD1 regulates transcription elongation and start site selection. While NAS is weaker than IMP/IDA evidence, this annotation complements more mechanistic terms.

Summary: IDA evidence from direct observation of CHD1 in SAGA complex architecture and function. CHD1 is component of SAGA transcription coactivator complex regulating Pol II transcription.

Reason: CHD1 is documented component of SAGA complex, which functions in RNA Pol II transcription regulation. IDA evidence confirms regulatory role in transcription.

Summary: CHD1 supports homologous recombination-based DSB repair through chromatin remodeling that facilitates access to DNA break sites and recruitment of repair factors (MRX, Exo1). IMP evidence from experimental perturbation demonstrates functional requirement.

Reason: Core biological process beyond transcription. CHD1 ATPase activity is required for efficient DSB end resection and HR repair. IMP evidence is strong.

Summary: IMP evidence from same study demonstrates CHD1 is required for DNA end resection (initial DSB processing step). CHD1 functions upstream of HR repair pathway.

Reason: Core molecular function in DNA repair. CHD1 enables initial step (end resection) required for HR repair. IMP evidence demonstrates functional requirement.

Summary: IDA evidence from biochemical characterization showing CHD1 reconfigures nucleosome structure. This is foundational evidence for CHD1's chromatin remodeling activity.

Reason: Core biological process. CHD1 is paradigmatic chromatin remodeler. IDA evidence is from foundational 2000 study establishing CHD1 function.

Summary: IDA evidence shows CHD1 localizes to and is active at DSB sites. CHD1 directly functions at chromatin adjacent to DSBs.

Reason: CHD1 is recruited to DSB sites where it functions in chromatin opening and repair factor recruitment. This correctly identifies cellular localization during DNA repair response.

Summary: Redundant with IBA and IEA ATP-dependent chromatin remodeler activity annotations (lines 3 and 22). IDA evidence from biochemical experiments provides strongest direct evidence.

Reason: This is a duplicate with stronger evidence (IDA from biochemical experiments). Multiple evidence sources (IBA, IEA, IDA) converge on this core function with IDA being strongest.

Summary: Redundant with preceding IDA chromatin remodeling annotation (from PMID:10811623). IDA evidence from recent cryo-EM structural study provides additional direct evidence for chromatin remodeling mechanism.

Reason: This is a duplicate. Multiple IDA studies from different experimental approaches (biochemical, structural) converge on core chromatin remodeling function.

Summary: Redundant with multiple ATP-dependent chromatin remodeler activity annotations (IBA line 3, IEA line 22, IDA line 39). Additional IDA evidence from structural characterization of catalytic mechanism.

Reason: Multiple redundant annotations of core function with converging evidence (IBA, IEA, multiple IDA). IDA from cryo-EM provides strongest mechanistic detail.

Summary: Redundant with IBA chromatin annotation (line 4). IDA evidence from direct localization study confirms CHD1 localizes to chromatin during transcription and transcription termination.

Reason: This is a duplicate of IBA annotation with converging evidence. IDA demonstrates direct chromatin localization during transcription processes.

Summary: Redundant with chromatin localizations above. IDA evidence shows CHD1 associates with transcribed chromatin regions.

Reason: Multiple IDA annotations confirm chromatin localization. This represents convergent direct evidence for same cellular component.

Summary: CHD1 binds to promoter regions and cis-regulatory elements where it functions in transcription start site selection and regulation. IDA evidence from ChIP-seq localization.

Reason: CHD1 localizes to promoters and transcription start sites. This reflects recruitment through specific chromatin features and DNA binding capability at regulatory regions.

Summary: IMP evidence demonstrates CHD1 regulates cohesin function, a protein complex required for sister chromatid cohesion during cell division. CHD1 maintains specific chromatin structures required for cohesin activity.

Reason: CHD1 participates in sister chromatid cohesion through cohesin regulation, but this is likely a secondary consequence of CHD1's nucleosome positioning activity rather than primary function. Not core to CHD1 catalytic mechanism.

Summary: HDA (homology-based annotation) suggests CHD1 localizes to mitochondria based on sequence homology or protein complex composition. However, CHD1 is primarily a nuclear protein. Multiple experimental studies show nuclear localization with no evidence of mitochondrial function.

Reason: CHD1 is an ATP-dependent chromatin remodeler functioning specifically in nuclear chromatin organization and transcription. No published evidence documents CHD1 mitochondrial localization or function. Likely annotation error from proteome annotation in this HDA source.

Summary: Redundant mitochondrion annotation with same weak evidence basis (HDA from proteome). Same problematic annotation as preceding entry.

Reason: No evidence for CHD1 mitochondrial localization. This is likely proteomics annotation artifact. All evidence supports exclusive nuclear localization. Remove redundant incorrect annotation.

Summary: IPI evidence documents CHD1 interaction with transcription elongation factors (Spt4, Spt5, Spt16, Pob3). CHD1 directly functions in transcription elongation process.

Reason: Core biological process. CHD1 is directly recruited to elongating polymerase complexes through elongation factor interactions. IPI evidence appropriately demonstrates functional association.

Summary: Redundant with multiple nucleosome organization annotations (IBA line 4, IEA line 21). IMP evidence from foundational study demonstrates experimental requirement for nucleosome organization function.

Reason: Multiple converging evidence sources (IBA, IEA, IMP) demonstrate CHD1's core nucleosome organization function. IMP provides direct experimental evidence.

Summary: IMP evidence shows CHD1 regulates chromatin structure. CHD1 works with ISW1 remodeler to establish nucleosome positioning and prevent histone exchange.

Reason: CHD1 positively regulates proper chromatin organization through nucleosome spacing and positioning. Distinct from direct chromatin remodeling (GO:0006338) - this captures regulatory role.

Summary: IDA evidence confirms CHD1 is a component of the SAGA transcription coactivator complex, originally identified through co-immunoprecipitation and mass spectrometry (PMID:15647753). CHD1 membership in SAGA is well established and not disputed. Note that whether the Chd1 chromodomain directly reads H3K4me3 to mediate SAGA recruitment is contested in the yeast literature (see GO:0140002 review); this cellular-component annotation does not depend on, and should not be taken to assert, direct H3K4me3 binding by the Chd1 chromodomain.

Reason: CHD1 is documented subunit of SAGA transcription coactivator complex. This is core cellular component context for transcriptional regulation function.

Summary: IDA evidence from ChIP studies shows CHD1 binds ribosomal DNA (rDNA) at transcribed regions. CHD1 functions in nucleosome organization at rRNA genes transcribed by RNA Pol I.

Reason: CHD1 localizes to rDNA chromatin and functions in nucleosome positioning at ribosomal RNA genes. Specific binding to rDNA is documented.

Summary: IGI evidence from genetic interaction studies demonstrates CHD1 regulates transcriptional start site (TSS) selection through nucleosome positioning at promoters. CHD1 interaction with Set2 histone methyltransferase coordinates TSS positioning.

Reason: CHD1 maintains nucleosome positioning at promoters that determines TSS selection. IGI evidence appropriately captures this specialized transcription regulation function.

Summary: Redundant with IBA DNA binding annotation (line 7). IDA evidence from crystallographic characterization of DNA-binding domain confirms direct DNA binding capability.

Reason: This is a duplicate with stronger evidence (IDA from structural studies). Both IBA and IDA confirm DNA binding as core molecular function.

Summary: IGI evidence from genetic interaction studies shows CHD1 functions in RNA Pol I transcription termination. CHD1 associates with rDNA and regulates nucleosome organization affecting termination.

Reason: CHD1 functions in rRNA gene regulation including termination of Pol I transcription through nucleosome positioning effects.

Summary: Redundant with preceding IPI transcription elongation annotation (same GO, same PMID, different evidence code). IGI evidence from genetic interaction complements IPI protein interaction evidence.

Reason: This is a duplicate of preceding annotation. Both IGI and IPI evidence from same study demonstrate CHD1 function in transcription elongation.

Summary: IMP evidence demonstrates CHD1 is functionally required for proper RNA Pol II transcription termination. CHD1 prevents read-through transcription and enables normal termination through chromatin remodeling.

Reason: CHD1 functions in transcription termination. IMP evidence demonstrates requirement for proper termination events.

Summary: Redundant with preceding IMP termination annotation (same GO, same PMID). IGI evidence provides additional genetic interaction support.

Reason: Duplicate annotation with convergent IMP and IGI evidence from same study supporting CHD1 role in transcription termination.

Summary: IDA evidence from foundational biochemical study shows CHD1 exhibits ATP-dependent catalytic activity on DNA substrate. This is appropriately general term encompassing CHD1's ATPase activity.

Reason: CHD1 catalyzes ATP-dependent DNA translocations and nucleosome repositioning. This appropriately general term complements more specific ATP hydrolysis and chromatin remodeler terms.

Summary: IDA evidence from ChIP studies shows CHD1 localizes to nucleolar chromatin (rDNA regions). CHD1 directly functions at nucleolar sites in rRNA gene transcription.

Reason: CHD1 localizes to and functions in nucleolar chromatin context. This appropriately specific cellular component reflects CHD1's rDNA association.

Summary: IDA evidence from localization studies demonstrates CHD1 binds chromatin DNA specifically in context of nucleosomes. This is more specific than generic DNA binding.

Reason: CHD1 binds DNA within chromatin context (not free DNA). This appropriately specific term distinguishes chromatin-DNA from unconstrained DNA binding.

Summary: IDA evidence confirms CHD1 is a component of SLIK complex (related to SAGA). CHD1 functions in SLIK-mediated transcriptional regulation and chromatin remodeling.

Reason: CHD1 is documented subunit of SLIK complex. This appropriately specific cellular component annotation complements SAGA complex annotation above.

Summary: This annotation is the subject of a genuine, unresolved conflict in the yeast literature. The annotation originates from a YEAST study: Pray-Grant et al. (PMID:15647753) reported that one of the two chromodomains of S. cerevisiae Chd1 specifically interacts with the H3K4 methylation mark, and they explicitly described this as "the first chromodomain that recognizes methylated histone H3 (Lys 4)". This was therefore primary yeast research, NOT a transfer of mammalian-style reader activity onto the yeast protein. However, subsequent structural and biochemical studies challenged this conclusion: Flanagan et al. (2005/2007) reported that the tandem chromodomains of S. cerevisiae Chd1 lack the aromatic cage required for methyl-lysine recognition and do not bind H3K4me3 (unlike human CHD1), and the falcon-cited genome-wide work of Lee et al. 2017 likewise concludes that yeast Chd1 does not directly bind H3K4me3 and instead maintains H3K4me3/H3K36me3 domain boundaries indirectly via recruitment by transcription elongation factors. The original H3K4me3-dependent acetylation result has been attributed to indirect effects rather than direct chromodomain reading. Because the two sides of this conflict remain genuinely contested, the molecular-function assignment cannot be confidently affirmed or removed on current evidence.

Reason: The evidence on direct H3K4me3 reader activity of the S. cerevisiae Chd1 chromodomain is genuinely contested and cannot be resolved from the available literature. On one side, the original yeast study (PMID:15647753) reported that a Chd1 chromodomain "specifically interacts with the methylated lysine 4 mark on histone H3" and described it as "the first chromodomain that recognizes methylated histone H3 (Lys 4)" - so this annotation arose from yeast research and is not a mammalian over-transfer. On the other side, later structural/biochemical work (Flanagan et al. 2005/2007) found that the yeast Chd1 chromodomains lack the aromatic cage and do not bind H3K4me3 (in contrast to human CHD1), and the falcon-cited Lee et al. 2017 genome-wide study reports that yeast Chd1 does not directly bind H3K4me3, attributing the original mark-dependence to indirect effects. Given this unresolved conflict between primary studies, the appropriate action is UNDECIDED rather than a confident accept or removal.

Summary: IGI evidence from genetic interaction screen shows CHD1 negatively regulates DNA replication. CHD1 and Set2 methyltransferase cooperatively inhibit replication initiation at certain sites/conditions.

Reason: CHD1 participates in replication regulation through genetic interactions with Set2, but this appears to be secondary consequence of chromatin organization function rather than primary catalytic role. Not core to CHD1's defined remodeling mechanism.