Existing Annotations Review

Core Functions

CHD1's defining molecular function - catalyzes ATP-dependent nucleosome repositioning and spacing through ATPase domain ratcheting mechanism and linker DNA binding via SANT/SLIDE domains

Molecular Function:

ATP-dependent chromatin remodeler activity

References

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

GO_REF:0000116

Automatic Gene Ontology annotation based on Rhea mapping

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10811623

The chromo domain protein chd1p from budding yeast is an ATP-dependent chromatin-modifying factor

PMID:12242279

RNA polymerase II elongation factors of Saccharomyces cerevisiae - a targeted proteomics approach

PMID:12504018

A role for chromatin remodeling in transcriptional termination by RNA polymerase II

PMID:12682017

Chromatin remodeling protein Chd1 interacts with transcription elongation factors and localizes to transcribed genes

PMID:14576278

The proteome of Saccharomyces cerevisiae mitochondria

PMID:14759368

High-definition macromolecular composition of yeast RNA-processing complexes

PMID:15647753

Chd1 chromodomain links histone H3 methylation with SAGA- and SLIK-dependent acetylation

PMID:16429126

Proteome survey reveals modularity of the yeast cell machinery

PMID:16554755

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae

PMID:16823961

Toward the complete yeast mitochondrial proteome - multidimensional separation techniques for mitochondrial proteomics

PMID:17259992

RNA polymerase I in yeast transcribes dynamic nucleosomal rDNA

PMID:18245327

A role for Chd1 and Set2 in negatively regulating DNA replication in Saccharomyces cerevisiae

PMID:19536198

An atlas of chaperone-protein interactions in Saccharomyces cerevisiae - implications to protein folding pathways in the cell

PMID:19948887

Histone H3K4 and K36 methylation, Chd1 and Rpd3S oppose the functions of Saccharomyces cerevisiae Spt4-Spt5 in transcription

PMID:20489023

A global protein kinase and phosphatase interaction network in yeast

PMID:21179020

Defining the budding yeast chromatin-associated interactome

PMID:21623345

The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT and SLIDE domains

PMID:21940898

A role for Snf2-related nucleosome-spacing enzymes in genome-wide nucleosome organization

PMID:22922743

Chromatin remodelers Isw1 and Chd1 maintain chromatin structure during transcription by preventing histone exchange

PMID:23468649

ISWI and CHD chromatin remodelers bind promoters but act in gene bodies

PMID:25216679

Architecture of the Saccharomyces cerevisiae SAGA transcription coactivator complex

PMID:26861626

The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo

PMID:31222142

The chromatin remodeler Chd1 regulates cohesin in budding yeast and humans

PMID:33174727

Yeast Chd1p Unwraps the Exit Side DNA upon ATP Binding to Facilitate the Nucleosome Translocation Occurring upon ATP Hydrolysis

PMID:34520455

The chromatin remodeler Chd1 supports MRX and Exo1 functions in resection of DNA double-strand breaks

PMID:37968396

The social and structural architecture of the yeast protein interactome

file:yeast/CHD1/CHD1-deep-research-perplexity.md

Deep research report on CHD1

📚 Additional Documentation

Deep Research Perplexity

(CHD1-deep-research-perplexity.md)

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organism: yeast
gene_id: CHD1
gene_symbol: CHD1
uniprot_accession: P32657
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gene_info: Name=CHD1; OrderedLocusNames=YER164W; ORFNames=SYGP-ORF4;
organism_full: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
protein_family: Belongs to the SNF2/RAD54 helicase family. .
protein_domains: Cdh1_DBD. (IPR041150); CHD1-2/Hrp3_HTH. (IPR056302); CHD1-like_C.
(IPR025260); Chromo-like_dom_sf. (IPR016197); Chromo/chromo_shadow_dom. (IPR000953)
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P32657
Protein Description: RecName: Full=Chromo domain-containing protein 1; EC=3.6.4.- {ECO:0000269|PubMed:10811623, ECO:0000269|PubMed:17949749}; AltName: Full=ATP-dependent helicase CHD1;
Gene Information: Name=CHD1; OrderedLocusNames=YER164W; ORFNames=SYGP-ORF4;
Organism (full): Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
Protein Family: Belongs to the SNF2/RAD54 helicase family. .
Key Domains: Cdh1_DBD. (IPR041150); CHD1-2/Hrp3_HTH. (IPR056302); CHD1-like_C. (IPR025260); Chromo-like_dom_sf. (IPR016197); Chromo/chromo_shadow_dom. (IPR000953)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "CHD1" matches the protein description above
Verify the organism is correct: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'CHD1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene CHD1 (gene ID: CHD1, UniProt: P32657) in yeast.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Let me analyze the user's query carefully. They are asking for a comprehensive research report on the CHD1 gene from yeast (Saccharomyces cerevisiae), with UniProt accession P32657.

The critical context provided states:
- UniProt Accession: P32657
- Protein Description: Chromo domain-containing protein 1 (CHD1)
- Gene: CHD1; ORFNames: SYGP-ORF4
- Organism: Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
- Protein Family: SNF2/RAD54 helicase family
- Key Domains: Cdh1_DBD, CHD1-2/Hrp3_HTH, CHD1-like_C, Chromo-like_dom_sf, Chromo/chromo_shadow_dom

I need to verify this is the correct gene and then provide a detailed research report about its function.

Looking at the search results provided, I can see extensive literature on CHD1 from yeast:
- [1], [2], [5], [6], [7], [8], [9], [10], [13], [14], [15], [17], [20], [26], [27], [28], [31], etc. all discuss yeast CHD1
- The organism is clearly Saccharomyces cerevisiae
- It's described as an ATP-dependent chromatin remodeling factor

So the gene symbol matches, the organism is correct, and the family information aligns. I should proceed with the research.

Key topics I need to cover based on the search results and the user's interests:

Primary Function:
ATP-dependent nucleosome remodeling factor
Catalyzes nucleosome repositioning and spacing
Involved in transcription elongation
Structural domains and their functions:
Paired chromodomains at the N-terminus that recognize histone modifications
SNF2-related ATPase domain providing catalytic activity
SANT and SLIDE domains for DNA binding
Biochemical mechanism:
ATP hydrolysis coupled to DNA translocation
Nucleosome unwrapping
Nucleosome sliding
Biological processes:
Transcription elongation
Nucleosome spacing and positioning
DNA repair
Chromatin organization
Cellular localization: Nuclear
Interactions:
Transcription elongation factors (Rt...)
FACT histone chaperone complex
Paf1 complex
Other remodeling factors (Isw1, Isw2)
Recent structural insights: Cryo-EM structures from 2017-2018 and 2025

I'm planning to write a comprehensive review organized into major sections covering protein structure, catalytic mechanisms, transcription elongation roles, nucleosome organization, factor interactions, and DNA repair functions. The structure will include a title, summary, and detailed sections with proper citations to support each topic area.

My outline includes sections on molecular architecture, remodeling activity, transcription elongation, nucleosome spacing, chromatin factor interactions, DNA repair, genomic localization patterns, disease relevance, evolutionary conservation, and concluding remarks. I need to ensure the final document reaches at least 10,000 words with well-integrated citations throughout.

Comprehensive Functional Annotation of CHD1: An ATP-Dependent Chromatin Remodeling Factor in Saccharomyces cerevisiae

The chromodomain-helicase DNA-binding protein 1 (CHD1) represents a critical ATP-dependent chromatin remodeling enzyme that functions as a monomeric protein in Saccharomyces cerevisiae, distinguished by its dual chromodomains, an SNF2-related ATPase catalytic core, and a C-terminal DNA-binding domain comprising SANT and SLIDE motifs[1][9]. This enzyme has emerged as a central regulator of chromatin architecture during transcription elongation, maintaining proper nucleosome positioning and spacing while facilitating the passage of RNA polymerase II through nucleosomal obstacles. The discovery of high-resolution cryo-electron microscopy structures between 2017 and 2025 has provided unprecedented molecular insight into how CHD1 engages nucleosomes and executes its remodeling activities, revealing that the protein uses ATP hydrolysis to selectively unwrap nucleosomal DNA and translocate the histone octamer along the DNA template[7][10]. Beyond transcription, CHD1 participates in homologous recombination-based DNA repair, assists in establishing proper heterochromatin structure, and maintains boundaries between distinct histone modification domains that regulate gene expression patterns. The functional specialization of CHD1 demonstrates remarkable evolutionary conservation across eukaryotic organisms, with humans expressing nine CHD family members that diverged into distinct subfamilies with partially overlapping yet specialized functions.

Protein Architecture and Structural Organization

Domains and Their Arrangement

CHD1 is constructed from several evolutionarily conserved functional domains arranged in a specific three-dimensional architecture that enables its multifaceted regulatory functions[6][9][14]. The protein spans approximately 1,274 amino acids in yeast and contains its defining structural elements arranged from the N-terminus to C-terminus as follows: a pair of tandem chromodomains at the N-terminus, a central SNF2-related helicase domain containing conserved ATP-binding and catalytic motifs, a helicase C domain, and a C-terminal DNA-binding domain[9][31]. The double chromodomains, which are characteristic of all CHD proteins, serve as regulatory platforms that mediate interactions with chromatin components and influence the overall conformational state of the enzyme[14]. These chromodomains, while present in yeast CHD1, do not bind to methylated histone H3K4 as they do in human CHD1, representing a notable divergence in substrate recognition mechanisms between yeast and mammalian orthologues[12][31].

The catalytic ATPase domain is remarkably conserved across all SNF2-family chromatin remodelers and consists of two tandem RecA-like folds containing seven conserved helicase-related sequence motifs that classify the enzyme within Superfamily 2 (SF2) of helicase-like proteins[17][39]. However, unlike true helicases, CHD1 and its SNF2-family relatives cannot separate nucleic acid strands in the manner characteristic of classical helicases; rather, they couple ATP hydrolysis to mechanical rearrangement of nucleosomal structure[17]. The two lobes of the ATPase domain undergo a characteristic ratcheting motion during the catalytic cycle that drives DNA translocation, with the lobes containing additional helices and structural protrusions not found in single-strand translocases, enabling the simultaneous engagement with both DNA strands of the nucleosomal DNA[42][58].

The C-terminal DNA-binding domain revealed through crystallographic studies contains structural homology to SANT and SLIDE domains previously identified in ISWI remodeling enzymes[6][17]. These domains function as a DNA-binding module that engages extranucleosomal DNA flanking the nucleosome core particle, with the SLIDE domain particularly important for nucleosome spacing activity[6][56]. The SANT domain provides histone-binding capacity found in ISWI remodelers, though CHD1 exhibits relatively minimal direct contacts with histone proteins and instead relies predominantly on DNA interactions to achieve nucleosome repositioning[34][58]. Between the ATPase motor and DNA-binding domain lies a polypeptide segment containing residues critical for coupling nucleosome-stimulated ATP hydrolysis to productive nucleosome sliding, as demonstrated through systematic mutagenesis studies[8].

Structural Conformational Changes Upon Nucleosome Binding

The cryo-EM structures of CHD1 bound to nucleosomes have revealed dramatic conformational reorganization that occurs as the enzyme transitions from its solution state to an active, nucleosome-engaged state[7][10][15][24]. In the apo state before nucleosome engagement, the tandem chromodomains present a relatively open configuration that physically impedes DNA binding to the ATPase domains, effectively maintaining the enzyme in an auto-inhibited state[24]. Upon nucleosome binding in the presence of ATP or non-hydrolyzable ATP analogues, the chromodomains undergo an approximately 18-degree rotation relative to their orientation in crystal structures of the isolated catalytic core[10][15]. This repositioning orients chromodomain I toward the nucleosomal DNA at superhelical location -1 (SHL-1), enabling productive engagement with the nucleosome surface[10][34].

The DNA-binding domain similarly undergoes substantial repositioning during this transition, moving from a peripheral position in the apo state to a configuration where the SANT and SLIDE domains bind tightly to the first 10 base pairs of linker DNA immediately adjacent to the nucleosome core particle[24][55]. This engagement of extranucleosomal DNA is functionally critical, as studies utilizing artificially constrained linker DNA demonstrate that nucleosome sliding is directed toward the longer linker when choices are available, and the DNA-binding domain affinity for extranucleosomal DNA constitutes the primary determinant of remodeling directionality[56]. Importantly, the conformational changes observed upon nucleosome binding are mechanistically connected, with the repositioning of chromodomains linked through the central ATPase domains to enable closure of the ATPase catalytic pocket, bringing conserved residues into alignment for ATP hydrolysis[34][42][58].

Catalytic Mechanism and Nucleosome Remodeling Activity

ATP Hydrolysis-Coupled DNA Unwrapping

The mechanism of nucleosome remodeling by CHD1 involves a sophisticated coupling of ATP hydrolysis to mechanical manipulation of the nucleosomal DNA structure[7]. High-resolution cryo-EM structures obtained at 4.8 Ångstrom resolution with transition state-mimicking compounds such as ADP·BeF₃ have captured CHD1 in a state poised for catalysis, revealing that two complete turns of DNA at superhelical locations -5 to -7 become detached from the histone octamer surface as the enzyme engages the nucleosome[7]. This DNA unwrapping fundamentally alters the trajectory of extranucleosomal DNA by approximately 60 degrees and disrupts DNA interactions with histone proteins H2A, H2B, and H3 that normally stabilize the wrapped configuration[7][53].

The unwrapping of nucleosomal DNA at the entry side of the nucleosome is nucleotide-dependent, requiring the binding of ATP or ATP analogues to proceed[7][15][53]. Biochemical experiments demonstrate that ATP binding to yeast CHD1 induces transient unwrapping of DNA on the exit side of the nucleosome, with this unwrapping specifically facilitating nucleosome translocation[50]. The process differs fundamentally from histone octamer ejection or histone variant exchange, as the histone octamer itself remains intact during CHD1-mediated remodeling and adopts only minimal conformational changes in comparison to remodeling complexes such as ACF[7]. This preservation of histone octamer integrity underscores CHD1's role as a nucleosome spacing enzyme rather than a nucleosome disruption or assembly factor.

Ratcheting Mechanism and DNA Translocation

The mechanism driving nucleosome repositioning involves a ratcheting cycle of the two lobes of the ATPase domain that moves along the DNA template in a directional manner[7][42]. The first DNA gyre at the entry side becomes engaged by the ATPase motor at superhelical location (SHL) +2, where motifs within lobe one contact one DNA strand while motifs within lobe two contact the opposing strand[42][58]. This bifurcated engagement with both strands enables the ATPase lobes to grip the DNA and drive its translocation toward the nucleosome dyad through conformational changes driven by ATP hydrolysis[42][58]. In contrast to the related Snf2 ATPase structure, CHD1 contacts DNA at specific motifs (motifs II and III within lobe one) that contact the opposite DNA strand, and these motifs undergo a similar ratcheting motion that would be anticipated to drive nucleosomal DNA movement[42].

The histone H4 tail plays an essential regulatory role in this catalytic process, with deletion or mutation of the H4 N-terminal tail substantially reducing both nucleosome sliding activity and ATPase activity[15][18]. Specifically, conserved acidic residues D729 and E669 in CHD1 contact the H4 tail, and these contacts are conserved across multiple classes of remodeling enzymes, suggesting a fundamental mechanistic principle[15]. The repositioning of ATPase lobe II upon ATP binding enables critical contacts with the histone H3 alpha-one helix and the histone H4 tail, stabilizing the nucleosome-bound enzyme in a catalytically competent state[15][34][58]. Furthermore, the interaction between the SANT and SLIDE DNA-binding domains with linker DNA is mechanistically coupled through the chromodomains to the ATP-dependent closure of the ATPase motor domains, providing molecular connectivity between linker DNA availability and motor domain activity that may regulate the rate of nucleosome movement[34][59].

Nucleosome Spacing and Periodic Array Formation

CHD1 possesses a characteristic activity to generate and maintain regularly spaced nucleosomal arrays with relatively constant spacing independent of nucleosome density, a property termed "clamping activity"[28]. In purified in vitro systems, CHD1 can convert irregularly spaced polynucleosomes into evenly spaced regular arrays with near-physiological repeat lengths of approximately 160-166 base pairs in S. cerevisiae[28][44]. This spacing activity is achieved through the protein's ability to slide nucleosomes and position them at defined intervals, distinct from the stochastic nucleosome deposition that occurs in the absence of active remodeling[25]. The SANT and SLIDE DNA-binding domains appear particularly important for this spacing function, as their removal substantially impairs the ability of CHD1 to generate ordered arrays, though complete loss of these domains does not entirely eliminate spacing activity[8][44].

Surprisingly, CHD1 generates constant nucleosome spacing even when the nucleosome density is experimentally reduced through removal of histone octamers, countering the long-held assumption that nucleosome spacing is simply determined by the proportion of histones relative to DNA[28]. This observation suggests that CHD1 maintains nucleosome spacing through an active mechanism involving protein-protein interactions between nucleosomes or indirect interactions mediated through the remodeler itself[28]. The mechanism may involve a "protein ruler" function where specific domain contacts with multiple nucleosomes simultaneously establish the spacing interval, though the precise molecular details remain to be fully elucidated. In genomic contexts, CHD1 maintains nucleosomal arrays with shorter spacing (approximately 159 base pairs in yeast) compared to the longer spacing established by ISW1 remodelers (approximately 175 base pairs), and these two remodeling enzymes compete on most genes to establish the final spacing observed in wild-type cells[25][60].

Role in Transcription Elongation and Chromatin Dynamics

Interactions with Elongation Factors and RNA Polymerase II Complex

CHD1 functions as an integral component of the transcription elongation machinery in S. cerevisiae through its direct physical and genetic interactions with multiple RNA polymerase II-associated factors[2][26][33][43]. The initial identification of CHD1 in two-hybrid screens with Rtf1, a component of the Paf1 complex (Paf1C) that travels with RNA polymerase II and regulates transcription elongation, established a functional connection between chromatin remodeling and transcription elongation[2][26]. Subsequently, co-immunoprecipitation studies confirmed that CHD1 interacts with critical elongation factors including the Spt4-Spt5 heterodimer (known as DSIF in mammals) and the Spt16-Pob3 complex (known as FACT in mammals), both of which function to facilitate RNA polymerase II passage through nucleosomal barriers[2][26][33].

Genetic analyses provide complementary evidence for CHD1's role in transcription elongation, as deletion of CHD1 suppresses cold-sensitive mutations in the elongation factor Spt5, and this suppression is shared with mutations affecting the Paf1 complex and RNA polymerase II itself[2][26]. Furthermore, a direct interaction has been identified between an N-terminal region of Rtf1 and the CHCT domain (a conserved domain within CHD1 about which little is known functionally) as being both necessary and sufficient for physical association, with mutations disrupting this interaction resulting in accumulation of CHD1 at the 5' ends of CHD1-occupied genes and increased cryptic transcription[13]. The conservation of this Rtf1-CHD1 interaction mechanism in mammalian systems, where homologous regions within mouse RTF1 interact with the CHCT domains of both mouse CHD1 and CHD2, suggests an evolutionarily conserved mechanism for coupling CHD family remodelers to transcription elongation complexes[13].

Nucleosome Repositioning During Transcription

Genome-wide chromatin immunoprecipitation studies demonstrate that CHD1 specifically localizes to the coding regions of actively transcribed genes, where it associates with the nucleosomes that must be traversed by RNA polymerase II during transcription elongation[2][26][43]. Importantly, CHD1 occupancy on gene bodies is partially dependent on Rtf1, the transcription elongation factor, suggesting that the elongation machinery actively recruits or retains CHD1 at transcribed chromatin regions[2][26]. The positioning of CHD1 on transcribed regions appears distinct from its role at promoters and transcription start sites, indicating that CHD1 carries out specialized functions during the elongation phase rather than transcription initiation.

A key function of CHD1 during transcription elongation involves re-establishing proper nucleosome positioning in the wake of RNA polymerase II passage[13][37]. As RNA polymerase II transcribes through chromatin, the transcription process inherently disrupts nucleosomal structure, causing nucleosomes to be pushed forward along the DNA template and potentially leading to displacement or disassembly of histone octamers if not actively managed[13][37]. CHD1 works coordinately with the FACT histone chaperone complex to resolve nucleosomal disruptions caused by transcription, with CHD1 promoting the translocation of FACT molecules from one nucleosome to the next along actively transcribed genes, enabling processive maintenance of chromatin integrity during transcription elongation[37][40]. The ATPase activity of CHD1 is critical for determining FACT distribution along genes, as catalytically inactive mutants of CHD1 phenocopy the effect of CHD1 deletion on FACT localization[37].

Effects on Histone Dynamics and Modification Patterns

Genome-wide analyses of histone turnover reveal that CHD1 exerts significant influence over the dynamics of histone H3 replacement, with the most prominent effects occurring at the 3' ends of genes rather than at promoters[51]. The effects of CHD1 on histone H3 turnover show gene-length dependence, with Chd1's influence on both 5' end and 3' end H3 turnover being greatest at unusually long genes and highly transcribed genes[51]. Mechanistically, CHD1 appears to stabilize nucleosomes that have been perturbed by transcription, preventing excessive turnover while simultaneously permitting the controlled replacement of histone variants and modified histones necessary for proper gene expression[51]. The influence of CHD1 on histone dynamics extends to changes in histone modification patterns genome-wide, with H3K36me3 in particular shifting its distribution pattern in concert with altered H3 replacement patterns in CHD1-deficient cells[51].

Nucleosome Organization and Chromatin Architecture

Suppression of Cryptic Transcription Through Nucleosome Positioning

One of the most striking consequences of CHD1 deletion is a dramatic increase in aberrant or cryptic transcription emanating from internal promoter sequences within coding regions[5][27]. This cryptic transcription arises not from reduced nucleosome occupancy genome-wide, as nucleosome abundance remains relatively constant in CHD1-deficient cells, but rather from loss of regular nucleosome positioning and phasing[5][27]. Specifically, nucleosome mapping studies in both S. cerevisiae and S. pombe reveal that CHD1 (or its fission yeast orthologues Hrp1 and Hrp3) is responsible for generating and maintaining transcription start site-aligned nucleosomal arrays throughout the genome with characteristic well-positioned nucleosomes immediately flanking nucleosome-free regions at promoters[27][44].

In CHD1-deficient cells, the loss of regularly positioned nucleosomes in gene coding regions presumably creates transiently accessible regions of chromatin that expose cryptic transcription initiation sites normally occluded by properly positioned nucleosomes[27]. Supporting this model, the addition of other mutations that affect nucleosome occupancy or histone modification patterns generates cryptic transcription through distinct mechanisms: deletion of the FACT complex subunit Pob3 reduces nucleosome occupancy without affecting nucleosome positioning, while deletion of the histone deacetylase Alp13 does not substantially alter nucleosome positioning or occupancy but increases histone acetylation that may recruit other remodeling factors[27]. These observations indicate that cryptic transcription can result from multiple distinct perturbations to chromatin structure, but when caused specifically by CHD1 deletion, it reflects defects in nucleosome positioning rather than occupancy.

Nucleosome-Free Regions and TSS Organization

The nucleosome-free region (NFR) typically observed at promoters, flanked by well-positioned +1 and -1 nucleosomes, requires coordinated action of multiple nucleosome remodeling enzymes in addition to sequence features[44][54]. In S. pombe, the two CHD-family remodelers Hrp1 and Hrp3 are individually responsible for generating nucleosome spacing in in vitro assays and are essential for maintaining genic nucleosomal arrays in vivo, yet neither single deletion causes complete loss of NFR formation at promoters[44]. This suggests that while CHD family remodelers are important for maintaining nucleosome arrays within genes, other mechanisms (potentially involving sequence-determined nucleosome positioning and other remodeling factors) contribute to NFR generation and maintenance at promoters. However, the combined deletion of both hrp1 and hrp3 severely compromises nucleosome positioning throughout the genome, demonstrating the essential collective role of CHD-family remodelers in establishing nucleosomal organization[44].

The positioning of nucleosomes relative to transcription start sites appears to influence transcriptional regulation independently of promoter accessibility, as experimental manipulation of the inter-nucleosome distance at specific heterochromatic loci reveals an oscillatory relationship between inter-nucleosome-free region distance and silencing efficiency[30]. This observation indicates that nucleosome positioning per se, beyond simple presence or absence of nucleosomes, contributes to the establishment and maintenance of repressive chromatin states, and proper nucleosome positioning may be necessary for robust gene silencing[30].

Interactions with Other Chromatin Remodeling Complexes

Redundancy and Competition with ISW1 and ISW2

CHD1 functions within a larger network of ATP-dependent chromatin remodeling activities that frequently exhibit functional redundancy yet maintain specialized roles in specific genomic contexts[5][25][27][45][60]. While individual deletion of CHD1 causes only subtle transcriptional changes and weak phenotypes, combined deletion of CHD1 with genes encoding other nucleosome spacing remodelers produces synthetic growth defects and severe defects in nucleosome positioning[5][14][27][45]. Specifically, yeast strains bearing combined deletions of chd1, isw1, and isw2 exhibit temperature sensitivity for growth and widespread disruption of nucleosome positioning, demonstrating substantial functional overlap among these spacing remodelers[5][14].

Genome-wide nucleosome sequencing studies reveal that CHD1 and ISW1 actively compete to set nucleosome spacing on most genes, with CHD1 establishing shorter spacing (approximately 159 base pairs) and ISW1 establishing longer spacing (approximately 175 base pairs)[25][60]. On heavily transcribed genes, nucleosome spacing is often extreme (either very short or very long), and these genes are specifically depleted of linker histone H1, which typically binds to longer spacing arrays to promote higher-order chromatin folding[25][60]. The hypothesis emerges that CHD1-specified short spacing evicts H1 and causes chromatin unfolding suitable for active transcription, whereas ISW1-specified longer spacing allows H1 binding and promotes chromatin condensation appropriate for more regulated transcription or inactive chromatin[25][60].

The competition between CHD1 and ISW1 appears dynamic across the genome, with the two remodelers potentially operating sequentially or concurrently on individual genes[25][60]. This dynamic competition provides a mechanism for fine-tuning nucleosome spacing in response to transcriptional activity and developmental cues. ISW2, another spacing remodeler, plays a more limited role restricted primarily to transcriptionally inactive genes, where it generates the longest spacing observed at any class of genes, suggesting a specialized function in establishing chromatin structure at silenced loci[60].

Cooperativity with SWI/SNF Complex

Genetic interactions between CHD1 and components of the SWI/SNF chromatin remodeling complex, which catalyzes nucleosome disruption rather than spacing, reveal additional layers of functional cooperation and potential antagonism[14][45][48]. Synthetic-lethal screening identified that combined mutations in CHD1 and SWI/SNF genes result in inviability, and similar temperature-sensitive synthetic growth defects arise from combined deletion of chd1 with mutations in the ISWI genes ISW1 and ISW2[14][45][48]. These genetic interactions strongly suggest that CHD1 and SWI/SNF maintain partially redundant functions in cell growth and nuclear organization, consistent with their distinct catalytic activities (nucleosome spacing versus disruption) operating toward the common goal of maintaining functional chromatin structure.

Importantly, the relationship between CHD1 and remodeling complexes is not simply one of redundancy but involves complex coordination of activities in specific biological contexts. For instance, CHD1 and FACT histone chaperone have been reported to act in opposition in regulating DNA replication, as chd1 and set2 mutations can suppress mutations in FACT components that cause sensitivity to hydroxyurea and other replication stresses[38]. This opposition appears to involve Chd1 negatively regulating DNA replication in a manner that differs from FACT's function in promoting replication fork progression[38].

Functions Beyond Transcription Elongation

DNA Repair and Homologous Recombination

Beyond its well-established roles in transcription and nucleosome organization, CHD1 participates in homologous recombination-based DNA double-strand break (DSB) repair through mechanisms that involve chromatin remodeling and chromatin opening at damage sites[19][22]. Both yeast and human CHD1 are recruited to chromatin adjacent to DSBs, where they promote the opening of chromatin and facilitate the recruitment of DNA repair factors[9][19][22]. Specifically, CHD1 promotes DSB repair through its effects on DNA end resection, the process by which the 5'-terminated DNA strands surrounding a DSB are degraded to generate single-stranded DNA overhangs necessary for homologous recombination[19][22].

In S. cerevisiae, CHD1 is required for efficient recruitment of the MRX complex (Mre11-Rad50-Xrs2) and the nuclease Exo1 to DSB ends, and deletion or catalytic inactivation of CHD1 reduces histone occupancy near DSB ends and substantially impairs DSB repair by homologous recombination[19]. The requirement for CHD1 ATPase activity demonstrates that the chromatin remodeling function, rather than structural roles of the protein, drives its contribution to DNA repair[19]. In human cells, targeted disruption of CHD1 leads to defects in early double-strand break signaling and homologous recombination, resulting in hypersensitivity to ionizing radiation as well as PARP and PTEN inhibition[22]. Furthermore, human CHD1 contains a unique N-terminal inhibitory region that represses the DNA-binding, ATPase, and chromatin assembly activities of the protein, and CHD1 lacking this N-terminal region is more active in rescuing defects in γH2AX formation and CtIP recruitment in CHD1-knockout cells[22].

The role of CHD1 in DNA repair appears conserved among the CHD protein family, as other family members including CHD2, CHD3, CHD4, and CHD7 have also been implicated in the cellular response to DNA damage, though with specialized roles in either homologous recombination or non-homologous end joining pathways[19]. Mutations in human CHD7 associated with CHARGE syndrome occur specifically in the SLIDE domain, the DNA-binding domain shared between Chd1 and ISWI remodelers[6], suggesting that defects in chromatin remodeling activity contribute to the disease phenotype.

Heterochromatin Assembly and Silencing

Chromodomain-containing proteins in general play important roles in heterochromatin assembly and transcriptional silencing, exemplified by the well-characterized role of the heterochromatin protein HP1 and the fission yeast protein Chp1[3][9]. While the yeast CHD1 chromodomains do not bind methylated histone H3K4 as occurs in mammalian CHD1 and other chromodomain proteins, CHD1 nonetheless participates in proper chromatin organization within heterochromatic domains and at telomeres[9]. The maintenance of nucleosome positioning in heterochromatic regions contributes to the stability of silenced chromatin states, as demonstrated by experiments altering the inter-nucleosome distance at heterochromatic loci, which causes corresponding oscillations in silencing efficiency[30].

Genomic Localization and Target Gene Selection

Association with Actively Transcribed Chromatin

Genome-wide chromatin immunoprecipitation followed by microarray analysis has established that yeast CHD1 specifically localizes to the coding regions of actively transcribed genes, with enrichment particularly pronounced within the transcribed regions rather than at promoters or transcription termination sites[2][26][43]. This localization pattern is consistent with CHD1's primary role in maintaining nucleosome positioning during transcription elongation rather than in transcription initiation. The association of CHD1 with transcribed chromatin appears partially dependent on Rtf1 and other components of the transcription elongation machinery, suggesting that active transcription and associated recruitment by elongation factors drive CHD1 targeting to specific genomic loci[2][26].

In contrast to human CHD1, which preferentially recognizes and binds histone H3K4me3 through its chromodomains as a mechanism for recruitment to active gene promoters, yeast Chd1 chromodomains do not directly recognize methylated histone H3K4[9][12][31]. Instead, yeast CHD1 appears to be recruited to genes through its interaction with the Paf1 complex and other elongation factors that physically associate with RNA polymerase II during transcription[2][26][43]. This divergence between yeast and mammalian CHD1 mechanisms for genomic targeting suggests that while the catalytic and regulatory logic of CHD family proteins has been conserved, the specific mechanisms for recruitment to genomic targets have been subject to evolutionary modification.

Biochemical Substrate Specificity

While CHD1 does not display obvious sequence-specific DNA-binding preferences, as its DNA-binding domain engages extranucleosomal DNA in a sequence-nonspecific manner, the enzyme does exhibit specificity for certain nucleosome substrate features[56]. CHD1 preferentially binds to and slides nucleosomes that possess longer extranucleosomal DNA (linker DNA), with this binding preference biasing the remodeler to shift histone octamers toward longer linker DNA, promoting nucleosome centering on short DNA fragments[56]. This preference for nucleosomes with longer linker DNA is shared with the related ISWI spacing remodelers, suggesting a conserved mechanism for directing nucleosome positioning that optimizes for nucleosome centering on small DNA molecules and regular spacing on genomic templates.

The nucleosome substrate specificity of CHD1 extends to histone modifications, as studies comparing nucleosome binding and remodeling activity on substrates with or without specific histone modifications reveal that H3K36 methylation, particularly the di- and tri-methylated forms that accumulate in actively transcribed gene bodies, influences CHD1 recruitment and activity[5][25][51]. Furthermore, the histone H4 acetylation state influences CHD1 activity at specific genomic loci, suggesting that both histone tail modifications and nucleosome density contribute to determining where and when CHD1 acts within the genome[5].

Protein Regulation and Structural Plasticity

Autoinhibitory Domains and Activation Mechanisms

The discovery that truncated forms of CHD1 lacking the first 57-88 amino acid residues or the entire N-terminal 133 amino acids show hyperactivity compared to full-length CHD1 indicates that N-terminal regions normally restrain the enzymatic activity of the protein through autoinhibitory mechanisms[24][55]. These hyperactive deletions also show reduced association between the ATPase motor and DNA-binding domain, suggesting that a more flexible linkage between these functional modules facilitates productive engagement with nucleosomes, while certain N-terminal residues maintain an autoinhibited state through interactions that maintain rigid positioning of the DNA-binding domain[24][55]. The fact that both enhanced activity mutants specifically reduce association between the ATPase and DNA-binding domain suggests that a less constrained positioning allows these domains to find optimal orientations for productive catalysis[24][55].

In human CHD1, an autoinhibitory N-terminal region distinct from the serine-rich region represses DNA-binding, ATP hydrolysis, and chromatin assembly and remodeling activities in vitro, though this region appears largely absent or divergent in yeast and Drosophila CHD1 proteins[22]. The repressive region of human CHD1 at the N-terminus is not conserved between human CHD1 and the closely related human CHD2, suggesting that the two closely related family members have evolved differential regulatory mechanisms for controlling their activity[22]. The identification of such autoinhibitory mechanisms suggests that CHD family remodelers may be subject to positive and negative regulation in response to cellular signals or post-translational modifications, though specific activators and inhibitors of CHD1 have not yet been definitively identified.

Nucleosome Substrate-Dependent Regulation

The regulation of CHD1 activity is intimately connected to the structural properties of its nucleosome substrates, as the linker DNA length available for interaction with the DNA-binding domain directly influences the rate of nucleosome movement[34][59]. The molecular connectivity between the positioning of the DNA-binding domain via the chromodomains to the ATPase catalytic pocket implies that linker DNA length directly regulates CHD1 activity, with longer linker DNA enabling more efficient closure of the ATPase motor domains and nucleotide binding[34][59]. This substrate-dependent regulation provides an elegant mechanism by which the spacing of nucleosomes genome-wide, which exhibits an average linker length of approximately 19 base pairs in S. cerevisiae, directly determines CHD1 catalytic efficiency and thus influence which genes CHD1 acts upon[34][59].

Summary of Molecular Functions and Mechanisms

The comprehensive picture of CHD1 function that emerges from structural, biochemical, and genomic studies reveals a highly specialized ATP-dependent chromatin remodeling enzyme whose primary catalytic function involves nucleosome sliding and spacing[1][2][5][7][8]. CHD1 executes this remodeling through a sophisticated molecular mechanism involving ATP-dependent ratcheting motion of ATPase lobes that translocates nucleosomal DNA toward the histone octamer dyad, coupled with substrate DNA-binding domains that engage extranucleosomal DNA to direct sliding toward longer linker DNA and promote nucleosome centering[7][34][42][56]. The enzyme operates predominantly as a monomeric protein and functions as a nucleosome-spacing enzyme rather than a nucleosome disruption or assembly factor, generating and maintaining regularly spaced nucleosomal arrays with constant spacing independent of nucleosome density[28][44].

Within the cell, CHD1 localizes to nuclei where it associates with transcribed chromatin through recruitment by transcription elongation factors including Rtf1 of the Paf1 complex and works coordinately with FACT histone chaperone to maintain nucleosome positioning and chromatin integrity as RNA polymerase II traverses the transcribed regions of genes[2][26][37][40]. Beyond transcription, CHD1 participates in homologous recombination-based DSB repair by promoting chromatin opening and the recruitment of nucleotide resection machinery[19][22]. The evolutionary conservation of CHD1 from yeast to humans, combined with the specialization of nine distinct CHD family members in mammals, underscores the fundamental importance of this remodeling activity for proper nuclear organization and gene regulation across eukaryotic organisms.

Conclusion

CHD1 stands as a paradigmatic example of an ATP-dependent chromatin remodeling factor whose sophisticated molecular architecture and dynamic regulatory mechanisms enable precise control of nucleosome positioning and spacing throughout the yeast genome. The monomeric architecture of yeast CHD1, contrasting with the multi-subunit complexes formed by other remodeling enzymes, provides a simplified yet comprehensive model system for understanding chromatin remodeling principles that apply broadly to all SNF2-family chromatin remodelers. The cryo-electron microscopy structures determined between 2017 and 2025 have provided unprecedented molecular detail into how CHD1 engages nucleosomes through the coordinated positioning of its functional domains to achieve DNA unwrapping and translocation, establishing mechanistic principles likely applicable to the broader family of related enzymes.

The functional diversity of CHD1 extends far beyond simple nucleosome repositioning to encompass roles in transcription elongation, homologous recombination DNA repair, heterochromatin maintenance, and epigenetic regulation through its effects on histone dynamics and modification patterns[1][9][13][19][22][51]. The remarkable evolutionary conservation of CHD protein domains and mechanisms across eukaryotic phyla, coupled with the specialization of mammalian CHD family members into distinct subfamilies with overlapping yet specialized functions, reflects the fundamental necessity of precise chromatin regulation for proper nuclear organization and gene expression in complex organisms. Future investigations into post-translational modification of CHD1, additional protein-protein interactions, and mechanisms regulating the autoinhibitory domains will likely reveal additional layers of regulation controlling when and where this crucial chromatin remodeling enzyme acts within the nuclear environment. The clinical significance of CHD1 mutations in human disease, particularly in prostate cancer development where CHD1 is mutated or deleted in approximately 10% of cases, underscores the importance of understanding this protein's cellular functions and the consequences of its dysregulation in pathological contexts.

Citations

https://www.yeastgenome.org/locus/S000000966
https://pmc.ncbi.nlm.nih.gov/articles/PMC154471/
https://pmc.ncbi.nlm.nih.gov/articles/PMC522800/
https://www.ncbi.nlm.nih.gov/gene/856911
https://pmc.ncbi.nlm.nih.gov/articles/PMC3560298/
https://pdbj.org/mine/summary/2XB0
https://pmc.ncbi.nlm.nih.gov/articles/PMC5697743/
https://pmc.ncbi.nlm.nih.gov/articles/PMC3243530/
https://en.wikipedia.org/wiki/CHD1
https://elifesciences.org/articles/35720
https://www.uniprot.org/uniprotkb/P32657/entry
https://pmc.ncbi.nlm.nih.gov/articles/PMC1421377/
https://pmc.ncbi.nlm.nih.gov/articles/PMC12390759/
https://pmc.ncbi.nlm.nih.gov/articles/PMC1899158/
https://pmc.ncbi.nlm.nih.gov/articles/PMC6118821/
https://pmc.ncbi.nlm.nih.gov/articles/PMC4162295/
https://royalsocietypublishing.org/rstb/article/372/1731/20160284/23281/The-tale-of-a-tail-histone-H4-acetylation-and-the
https://pmc.ncbi.nlm.nih.gov/articles/PMC8462745/
https://pmc.ncbi.nlm.nih.gov/articles/PMC230505/
https://academic.oup.com/nar/article/46/8/3891/4909984
https://elifesciences.org/articles/22510
https://www.science.org/doi/10.1126/sciadv.adw7108
https://pmc.ncbi.nlm.nih.gov/articles/PMC3492713/
https://pmc.ncbi.nlm.nih.gov/articles/PMC4387221/
https://pmc.ncbi.nlm.nih.gov/articles/PMC2099615/
https://www.pnas.org/doi/10.1073/pnas.2004111117
https://elifesciences.org/articles/35720.pdf
https://pubmed.ncbi.nlm.nih.gov/33174727/
https://pmc.ncbi.nlm.nih.gov/articles/PMC9149603/
https://pmc.ncbi.nlm.nih.gov/articles/PMC2248355/
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https://genesdev.cshlp.org/content/12/18/2956
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https://academic.oup.com/nar/article/38/5/1441/3112508
https://pmc.ncbi.nlm.nih.gov/articles/PMC4889916/

📄 View Raw YAML

id: P32657
gene_symbol: CHD1
aliases:
  - YER164W
  - SYGP-ORF4
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: |
  CHD1 (Chromatin Helicase DNA-binding protein 1) is an ATP-dependent chromatin remodeling enzyme
  that functions as a monomeric protein in yeast. It catalyzes nucleosome sliding and spacing through
  ATP hydrolysis, positioning nucleosomes into regular arrays with ~159 bp spacing. CHD1 contains
  paired N-terminal chromodomains, a central SNF2-related ATPase catalytic domain, and a C-terminal
  DNA-binding domain (SANT/SLIDE). During transcription elongation, CHD1 works with RNA Pol II elongation
  factors (Paf1, FACT) to maintain chromatin integrity as polymerase traverses nucleosomal obstacles.
  CHD1 also functions in DNA double-strand break repair, heterochromatin organization, and nucleosome
  spacing maintenance. Unlike mammalian CHD1, yeast CHD1 chromodomains do not bind H3K4me3; rather,
  CHD1 is recruited to genes via elongation factor interactions.
existing_annotations:
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:12682017
          supporting_text: Chromatin remodeling protein Chd1 interacts with 
            transcription elongation factors and localizes to transcribed genes
        - reference_id: PMID:10811623
          supporting_text: The chromo domain protein chd1p from budding yeast is
            an ATP-dependent chromatin-modifying factor
        - reference_id: file:yeast/CHD1/CHD1-deep-research-perplexity.md
          supporting_text: 'provider: perplexity'
  - term:
      id: GO:0042393
      label: histone binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: KEEP_AS_NON_CORE
      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).
      supported_by:
        - reference_id: PMID:12682017
          supporting_text: Chd1 also interacts with components of two essential 
            elongation factors, Spt4-Spt5 and Spt16-Pob3
  - term:
      id: GO:0140658
      label: ATP-dependent chromatin remodeler activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:10811623
          supporting_text: Biochemical experiments using Chd1p purified from 
            yeast showed that it reconfigures the structure of nucleosome core 
            particles
  - term:
      id: GO:0000785
      label: chromatin
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      reason: CHD1 acts directly on chromatin structures as a nucleosome 
        remodeling enzyme. This is a core cellular component context for all its
        functions.
      supported_by:
        - reference_id: PMID:12682017
          supporting_text: Chd1, Rtf1 and Spt5 associate with actively 
            transcribed regions of chromatin
  - term:
      id: GO:0034728
      label: nucleosome organization
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      reason: Core biological process function. CHD1 directly organizes 
        nucleosome spacing genome-wide through ATP-dependent sliding and 
        positioning.
      supported_by:
        - reference_id: PMID:10811623
          supporting_text: Chd1p functions as a nucleosome remodeling factor
  - term:
      id: GO:0016887
      label: ATP hydrolysis activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      reason: Core enzymatic activity. ATP hydrolysis is mechanistically coupled
        to nucleosome repositioning and spacing function.
      supported_by:
        - reference_id: PMID:10811623
          supporting_text: The chromo domain protein chd1p from budding yeast is
            an ATP-dependent chromatin-modifying factor
  - term:
      id: GO:0003677
      label: DNA binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      reason: Core molecular function. DNA binding is essential for 
        directionality and mechanism of nucleosome sliding. SANT/SLIDE domains 
        specifically recognize and bind linker DNA.
      supported_by:
        - reference_id: PMID:21623345
          supporting_text: The DNA-binding domain of the Chd1 
            chromatin-remodelling enzyme contains SANT and SLIDE domains
  - term:
      id: GO:0003682
      label: chromatin binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      reason: Core substrate interaction. CHD1 recognizes and binds to 
        nucleosomal chromatin as its primary functional substrate for 
        remodeling.
  - term:
      id: GO:0000123
      label: histone acetyltransferase complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      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.
      action: ACCEPT
      reason: CHD1 functions as a subunit of both SAGA and SLIK complexes. While
        IEA, this is supported by IDA evidence and literature.
      supported_by:
        - reference_id: PMID:15647753
          supporting_text: Chd1 chromodomain links histone H3 methylation with 
            SAGA- and SLIK-dependent acetylation
  - term:
      id: GO:0000166
      label: nucleotide binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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.
      action: ACCEPT
      reason: CHD1 binds ATP as substrate for catalytic activity. This is a 
        well-established molecular function directly linked to IBA-supported ATP
        hydrolysis activity.
  - term:
      id: GO:0003677
      label: DNA binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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.
      action: ACCEPT
      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).
  - term:
      id: GO:0005524
      label: ATP binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      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.
      action: ACCEPT
      reason: Core molecular function. ATP binding is essential for catalytic 
        activity and is clearly supported by domain structure and biochemical 
        evidence.
      supported_by:
        - reference_id: PMID:10811623
          supporting_text: The chromo domain protein chd1p from budding yeast is
            an ATP-dependent chromatin-modifying factor
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      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.
      action: ACCEPT
      reason: This is a duplicate of the IBA annotation. Both correctly identify
        nuclear localization using different evidence approaches (phylogenetic 
        vs. keyword mapping).
  - term:
      id: GO:0006325
      label: chromatin organization
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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.
      action: ACCEPT
      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.
  - term:
      id: GO:0006351
      label: DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:12682017
          supporting_text: Chromatin remodeling factor Chd1 functions during 
            transcription elongation
  - term:
      id: GO:0006366
      label: transcription by RNA polymerase II
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      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.
      action: ACCEPT
      reason: CHD1 is directly recruited by Paf1 complex components associated 
        with RNA Pol II and functions in Pol II-dependent transcription.
      supported_by:
        - reference_id: PMID:12682017
          supporting_text: First, we identified Chd1 in a two-hybrid screen for 
            proteins that interact with Rtf1, a member of the Paf1 complex that 
            associates with RNA pol II
  - term:
      id: GO:0010468
      label: regulation of gene expression
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      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.
      action: ACCEPT
      reason: CHD1 regulates transcription elongation and transcription start 
        site selection through nucleosome positioning. This appropriately 
        general term complements more specific process terms.
  - term:
      id: GO:0016787
      label: hydrolase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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.
      action: ACCEPT
      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.
  - term:
      id: GO:0016887
      label: ATP hydrolysis activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000116
    review:
      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.
      action: ACCEPT
      reason: This is a duplicate of the IBA annotation. Multiple evidence 
        sources (IBA, IEA via RHEA) confirm ATP hydrolysis as core function.
  - term:
      id: GO:0034728
      label: nucleosome organization
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Redundant with IBA GO:0034728 nucleosome organization (line 4). 
        IEA annotation from ARBA machine learning independently confirms CHD1's 
        role in nucleosome organization.
      action: ACCEPT
      reason: This is a duplicate of the IBA annotation. Multiple independent 
        evidence sources (IBA, IEA/ARBA) strongly support nucleosome 
        organization function.
  - term:
      id: GO:0140658
      label: ATP-dependent chromatin remodeler activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      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.
      action: ACCEPT
      reason: This is a duplicate of the IBA annotation. Multiple evidence 
        sources converge on this core function.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:12242279
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:12242279
          supporting_text: "Spt16/Pob3 was discovered to associate with three distinct
            complexes: histones; Chd1/casein kinase II (CKII)"
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:14759368
    review:
      summary: Additional IPI evidence for CHD1 protein interactions from 
        high-definition macromolecular composition studies. Same non-informative
        generic term as preceding annotation.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:14759368
          supporting_text: High-definition macromolecular composition of yeast 
            RNA-processing complexes.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16429126
    review:
      summary: IPI evidence for protein interactions from proteome survey of 
        yeast cell machinery. Same generic binding term.
      action: KEEP_AS_NON_CORE
      reason: Generic protein binding term from proteome-wide study. Specific 
        binding partners and functional consequences already captured in 
        transcription elongation and nucleosome organization annotations.
      supported_by:
        - reference_id: PMID:16429126
          supporting_text: Proteome survey reveals modularity of the yeast cell 
            machinery.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16554755
    review:
      summary: IPI evidence for protein complex interactions from global 
        landscape of protein complexes in yeast. Generic binding term.
      action: KEEP_AS_NON_CORE
      reason: Generic protein binding annotation from large-scale protein 
        complex study. Redundant with other protein binding IPI annotations.
      supported_by:
        - reference_id: PMID:16554755
          supporting_text: Global landscape of protein complexes in the yeast 
            Saccharomyces cerevisiae.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19536198
    review:
      summary: IPI evidence from chaperone-protein interactions atlas. Generic 
        binding term.
      action: KEEP_AS_NON_CORE
      reason: Generic protein binding from chaperone interaction study. 
        Consistent evidence pattern but non-specific term.
      supported_by:
        - reference_id: PMID:19536198
          supporting_text: 'An atlas of chaperone-protein interactions in Saccharomyces
            cerevisiae: implications to protein folding pathways in the cell.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20489023
    review:
      summary: IPI evidence from global protein kinase and phosphatase 
        interaction network. Generic binding term.
      action: KEEP_AS_NON_CORE
      reason: Generic protein binding from kinase/phosphatase study. 
        Non-informative generic term despite valid evidence.
      supported_by:
        - reference_id: PMID:20489023
          supporting_text: A global protein kinase and phosphatase interaction 
            network in yeast.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21179020
    review:
      summary: IPI evidence from chromatin-associated interactome study. Generic
        binding term.
      action: KEEP_AS_NON_CORE
      reason: Generic protein binding from chromatin interactome. Multiple IPI 
        annotations with same generic term should be consolidated to informative
        binding types.
      supported_by:
        - reference_id: PMID:21179020
          supporting_text: Defining the budding yeast chromatin-associated 
            interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:37968396
    review:
      summary: IPI evidence from recent social and structural architecture of 
        yeast protein interactome study. Generic binding term.
      action: KEEP_AS_NON_CORE
      reason: Generic protein binding from latest interactome study. Multiple 
        redundant IPI annotations should prioritize specific binding 
        interactions over generic protein binding.
      supported_by:
        - reference_id: PMID:37968396
          supporting_text: Nov 15. The social and structural architecture of the
            yeast protein interactome.
  - term:
      id: GO:0140750
      label: nucleosome array spacer activity
    evidence_type: IGI
    original_reference_id: PMID:21940898
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21940898
          supporting_text: A role for Snf2-related nucleosome-spacing enzymes in
            genome-wide nucleosome organization
  - term:
      id: GO:0140750
      label: nucleosome array spacer activity
    evidence_type: IMP
    original_reference_id: PMID:26861626
    review:
      summary: IMP evidence from direct experimental manipulation demonstrates 
        CHD1 sets nucleosome spacing in vivo. CHD1 and ISW1 compete to establish
        different spacing patterns.
      action: ACCEPT
      reason: Core molecular function directly demonstrated through experimental
        perturbation. IMP evidence is among strongest. CHD1 is a paradigmatic 
        nucleosome-spacing remodeler.
      supported_by:
        - reference_id: PMID:26861626
          supporting_text: The ISW1 and CHD1 ATP-dependent chromatin remodelers 
            compete to set nucleosome spacing in vivo
  - term:
      id: GO:0140750
      label: nucleosome array spacer activity
    evidence_type: IGI
    original_reference_id: PMID:26861626
    review:
      summary: IGI evidence from same study documenting genetic interaction 
        between CHD1 and ISW1 in nucleosome spacing. Redundant with IMP 
        annotation from same paper.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:26861626
          supporting_text: 2016 Feb 9. The ISW1 and CHD1 ATP-dependent chromatin
            remodelers compete to set nucleosome spacing in vivo.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: NAS
    original_reference_id: PMID:15647753
    review:
      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.
      action: ACCEPT
      reason: This is a redundant annotation with two stronger evidence sources 
        (IBA, IEA) already present. NAS is narrative assertion but conclusion is
        well-supported.
      supported_by:
        - reference_id: PMID:15647753
          supporting_text: Chd1 chromodomain links histone H3 methylation with 
            SAGA- and SLIK-dependent acetylation.
  - term:
      id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    evidence_type: NAS
    original_reference_id: PMID:15647753
    review:
      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.
      action: ACCEPT
      reason: CHD1 regulates transcription elongation and start site selection. 
        While NAS is weaker than IMP/IDA evidence, this annotation complements 
        more mechanistic terms.
      supported_by:
        - reference_id: PMID:15647753
          supporting_text: Chd1 chromodomain links histone H3 methylation with 
            SAGA- and SLIK-dependent acetylation
  - term:
      id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    evidence_type: IDA
    original_reference_id: PMID:25216679
    review:
      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.
      action: ACCEPT
      reason: CHD1 is documented component of SAGA complex, which functions in 
        RNA Pol II transcription regulation. IDA evidence confirms regulatory 
        role in transcription.
      supported_by:
        - reference_id: PMID:25216679
          supporting_text: Architecture of the Saccharomyces cerevisiae SAGA 
            transcription coactivator complex
  - term:
      id: GO:0000724
      label: double-strand break repair via homologous recombination
    evidence_type: IMP
    original_reference_id: PMID:34520455
    review:
      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.
      action: ACCEPT
      reason: Core biological process beyond transcription. CHD1 ATPase activity
        is required for efficient DSB end resection and HR repair. IMP evidence 
        is strong.
      supported_by:
        - reference_id: PMID:34520455
          supporting_text: The chromatin remodeler Chd1 supports MRX and Exo1 
            functions in resection of DNA double-strand breaks
  - term:
      id: GO:0000729
      label: DNA double-strand break processing
    evidence_type: IMP
    original_reference_id: PMID:34520455
    review:
      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.
      action: ACCEPT
      reason: Core molecular function in DNA repair. CHD1 enables initial step 
        (end resection) required for HR repair. IMP evidence demonstrates 
        functional requirement.
      supported_by:
        - reference_id: PMID:34520455
          supporting_text: The chromatin remodeler Chd1 supports MRX and Exo1 
            functions in resection of DNA double-strand breaks
  - term:
      id: GO:0006338
      label: chromatin remodeling
    evidence_type: IDA
    original_reference_id: PMID:10811623
    review:
      summary: IDA evidence from biochemical characterization showing CHD1 
        reconfigures nucleosome structure. This is foundational evidence for 
        CHD1's chromatin remodeling activity.
      action: ACCEPT
      reason: Core biological process. CHD1 is paradigmatic chromatin remodeler.
        IDA evidence is from foundational 2000 study establishing CHD1 function.
      supported_by:
        - reference_id: PMID:10811623
          supporting_text: Biochemical experiments using Chd1p purified from 
            yeast showed that it reconfigures the structure of nucleosome core 
            particles
  - term:
      id: GO:0035861
      label: site of double-strand break
    evidence_type: IDA
    original_reference_id: PMID:34520455
    review:
      summary: IDA evidence shows CHD1 localizes to and is active at DSB sites. 
        CHD1 directly functions at chromatin adjacent to DSBs.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:34520455
          supporting_text: The chromatin remodeler Chd1 supports MRX and Exo1 
            functions in resection of DNA double-strand breaks
  - term:
      id: GO:0140658
      label: ATP-dependent chromatin remodeler activity
    evidence_type: IDA
    original_reference_id: PMID:10811623
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:10811623
          supporting_text: The chromo domain protein chd1p from budding yeast is
            an ATP-dependent chromatin-modifying factor.
  - term:
      id: GO:0006338
      label: chromatin remodeling
    evidence_type: IDA
    original_reference_id: PMID:33174727
    review:
      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.
      action: ACCEPT
      reason: This is a duplicate. Multiple IDA studies from different 
        experimental approaches (biochemical, structural) converge on core 
        chromatin remodeling function.
      supported_by:
        - reference_id: PMID:33174727
          supporting_text: Yeast Chd1p Unwraps the Exit Side DNA upon ATP 
            Binding to Facilitate the Nucleosome Translocation Occurring upon 
            ATP Hydrolysis
  - term:
      id: GO:0140658
      label: ATP-dependent chromatin remodeler activity
    evidence_type: IDA
    original_reference_id: PMID:33174727
    review:
      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.
      action: ACCEPT
      reason: Multiple redundant annotations of core function with converging 
        evidence (IBA, IEA, multiple IDA). IDA from cryo-EM provides strongest 
        mechanistic detail.
      supported_by:
        - reference_id: PMID:33174727
          supporting_text: Epub 2020 Nov 11. Yeast Chd1p Unwraps the Exit Side 
            DNA upon ATP Binding to Facilitate the Nucleosome Translocation 
            Occurring upon ATP Hydrolysis.
  - term:
      id: GO:0000785
      label: chromatin
    evidence_type: IDA
    original_reference_id: PMID:12504018
    review:
      summary: Redundant with IBA chromatin annotation (line 4). IDA evidence 
        from direct localization study confirms CHD1 localizes to chromatin 
        during transcription and transcription termination.
      action: ACCEPT
      reason: This is a duplicate of IBA annotation with converging evidence. 
        IDA demonstrates direct chromatin localization during transcription 
        processes.
      supported_by:
        - reference_id: PMID:12504018
          supporting_text: A role for chromatin remodeling in transcriptional 
            termination by RNA polymerase II.
  - term:
      id: GO:0000785
      label: chromatin
    evidence_type: IDA
    original_reference_id: PMID:12682017
    review:
      summary: Redundant with chromatin localizations above. IDA evidence shows 
        CHD1 associates with transcribed chromatin regions.
      action: ACCEPT
      reason: Multiple IDA annotations confirm chromatin localization. This 
        represents convergent direct evidence for same cellular component.
      supported_by:
        - reference_id: PMID:12682017
          supporting_text: Chromatin remodeling protein Chd1 interacts with 
            transcription elongation factors and localizes to transcribed genes.
  - term:
      id: GO:0000976
      label: transcription cis-regulatory region binding
    evidence_type: IDA
    original_reference_id: PMID:23468649
    review:
      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.
      action: ACCEPT
      reason: CHD1 localizes to promoters and transcription start sites. This 
        reflects recruitment through specific chromatin features and DNA binding
        capability at regulatory regions.
      supported_by:
        - reference_id: PMID:23468649
          supporting_text: ISWI and CHD chromatin remodelers bind promoters but 
            act in gene bodies
  - term:
      id: GO:0007062
      label: sister chromatid cohesion
    evidence_type: IMP
    original_reference_id: PMID:31222142
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:31222142
          supporting_text: The chromatin remodeler Chd1 regulates cohesin in 
            budding yeast and humans
  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: HDA
    original_reference_id: PMID:14576278
    review:
      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.
      action: REMOVE
      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.
      supported_by:
        - reference_id: PMID:14576278
          supporting_text: The proteome of Saccharomyces cerevisiae 
            mitochondria.
  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: HDA
    original_reference_id: PMID:16823961
    review:
      summary: Redundant mitochondrion annotation with same weak evidence basis 
        (HDA from proteome). Same problematic annotation as preceding entry.
      action: REMOVE
      reason: No evidence for CHD1 mitochondrial localization. This is likely 
        proteomics annotation artifact. All evidence supports exclusive nuclear 
        localization. Remove redundant incorrect annotation.
      supported_by:
        - reference_id: PMID:16823961
          supporting_text: 'Toward the complete yeast mitochondrial proteome: multidimensional
            separation techniques for mitochondrial proteomics.'
  - term:
      id: GO:0006368
      label: transcription elongation by RNA polymerase II
    evidence_type: IPI
    original_reference_id: PMID:12682017
    review:
      summary: IPI evidence documents CHD1 interaction with transcription 
        elongation factors (Spt4, Spt5, Spt16, Pob3). CHD1 directly functions in
        transcription elongation process.
      action: ACCEPT
      reason: Core biological process. CHD1 is directly recruited to elongating 
        polymerase complexes through elongation factor interactions. IPI 
        evidence appropriately demonstrates functional association.
      supported_by:
        - reference_id: PMID:12682017
          supporting_text: Chd1 also interacts with components of two essential 
            elongation factors, Spt4-Spt5 and Spt16-Pob3
  - term:
      id: GO:0034728
      label: nucleosome organization
    evidence_type: IMP
    original_reference_id: PMID:10811623
    review:
      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.
      action: ACCEPT
      reason: Multiple converging evidence sources (IBA, IEA, IMP) demonstrate 
        CHD1's core nucleosome organization function. IMP provides direct 
        experimental evidence.
      supported_by:
        - reference_id: PMID:10811623
          supporting_text: The chromo domain protein chd1p from budding yeast is
            an ATP-dependent chromatin-modifying factor.
  - term:
      id: GO:1902275
      label: regulation of chromatin organization
    evidence_type: IMP
    original_reference_id: PMID:22922743
    review:
      summary: IMP evidence shows CHD1 regulates chromatin structure. CHD1 works
        with ISW1 remodeler to establish nucleosome positioning and prevent 
        histone exchange.
      action: ACCEPT
      reason: CHD1 positively regulates proper chromatin organization through 
        nucleosome spacing and positioning. Distinct from direct chromatin 
        remodeling (GO:0006338) - this captures regulatory role.
      supported_by:
        - reference_id: PMID:22922743
          supporting_text: Chromatin remodelers Isw1 and Chd1 maintain chromatin
            structure during transcription by preventing histone exchange
  - term:
      id: GO:0000124
      label: SAGA complex
    evidence_type: IDA
    original_reference_id: PMID:15647753
    review:
      summary: IDA evidence confirms CHD1 is a component of SAGA complex through
        co-immunoprecipitation and mass spectrometry. CHD1 chromodomain 
        specifically recognizes and binds histone H3 methylation marks important
        for SAGA recruitment.
      action: ACCEPT
      reason: CHD1 is documented subunit of SAGA transcription coactivator 
        complex. This is core cellular component context for transcriptional 
        regulation function.
      supported_by:
        - reference_id: PMID:15647753
          supporting_text: Chd1 chromodomain links histone H3 methylation with 
            SAGA- and SLIK-dependent acetylation
  - term:
      id: GO:0000182
      label: rDNA binding
    evidence_type: IDA
    original_reference_id: PMID:17259992
    review:
      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.
      action: ACCEPT
      reason: CHD1 localizes to rDNA chromatin and functions in nucleosome 
        positioning at ribosomal RNA genes. Specific binding to rDNA is 
        documented.
      supported_by:
        - reference_id: PMID:17259992
          supporting_text: RNA polymerase I in yeast transcribes dynamic 
            nucleosomal rDNA
  - term:
      id: GO:0001178
      label: regulation of transcriptional start site selection at RNA 
        polymerase II promoter
    evidence_type: IGI
    original_reference_id: PMID:19948887
    review:
      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.
      action: ACCEPT
      reason: CHD1 maintains nucleosome positioning at promoters that determines
        TSS selection. IGI evidence appropriately captures this specialized 
        transcription regulation function.
      supported_by:
        - reference_id: PMID:19948887
          supporting_text: Histone H3K4 and K36 methylation, Chd1 and Rpd3S 
            oppose the functions of Saccharomyces cerevisiae Spt4-Spt5 in 
            transcription
  - term:
      id: GO:0003677
      label: DNA binding
    evidence_type: IDA
    original_reference_id: PMID:21623345
    review:
      summary: Redundant with IBA DNA binding annotation (line 7). IDA evidence 
        from crystallographic characterization of DNA-binding domain confirms 
        direct DNA binding capability.
      action: ACCEPT
      reason: This is a duplicate with stronger evidence (IDA from structural 
        studies). Both IBA and IDA confirm DNA binding as core molecular 
        function.
      supported_by:
        - reference_id: PMID:21623345
          supporting_text: The DNA-binding domain of the Chd1 
            chromatin-remodelling enzyme contains SANT and SLIDE domains.
  - term:
      id: GO:0006363
      label: termination of RNA polymerase I transcription
    evidence_type: IGI
    original_reference_id: PMID:17259992
    review:
      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.
      action: ACCEPT
      reason: CHD1 functions in rRNA gene regulation including termination of 
        Pol I transcription through nucleosome positioning effects.
      supported_by:
        - reference_id: PMID:17259992
          supporting_text: RNA polymerase I in yeast transcribes dynamic 
            nucleosomal rDNA
  - term:
      id: GO:0006368
      label: transcription elongation by RNA polymerase II
    evidence_type: IGI
    original_reference_id: PMID:12682017
    review:
      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.
      action: ACCEPT
      reason: This is a duplicate of preceding annotation. Both IGI and IPI 
        evidence from same study demonstrate CHD1 function in transcription 
        elongation.
      supported_by:
        - reference_id: PMID:12682017
          supporting_text: Chromatin remodeling protein Chd1 interacts with 
            transcription elongation factors and localizes to transcribed genes.
  - term:
      id: GO:0006369
      label: termination of RNA polymerase II transcription
    evidence_type: IMP
    original_reference_id: PMID:12504018
    review:
      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.
      action: ACCEPT
      reason: CHD1 functions in transcription termination. IMP evidence 
        demonstrates requirement for proper termination events.
      supported_by:
        - reference_id: PMID:12504018
          supporting_text: A role for chromatin remodeling in transcriptional 
            termination by RNA polymerase II
  - term:
      id: GO:0006369
      label: termination of RNA polymerase II transcription
    evidence_type: IGI
    original_reference_id: PMID:12504018
    review:
      summary: Redundant with preceding IMP termination annotation (same GO, 
        same PMID). IGI evidence provides additional genetic interaction 
        support.
      action: ACCEPT
      reason: Duplicate annotation with convergent IMP and IGI evidence from 
        same study supporting CHD1 role in transcription termination.
      supported_by:
        - reference_id: PMID:12504018
          supporting_text: A role for chromatin remodeling in transcriptional 
            termination by RNA polymerase II.
  - term:
      id: GO:0008094
      label: ATP-dependent activity, acting on DNA
    evidence_type: IDA
    original_reference_id: PMID:10811623
    review:
      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.
      action: ACCEPT
      reason: CHD1 catalyzes ATP-dependent DNA translocations and nucleosome 
        repositioning. This appropriately general term complements more specific
        ATP hydrolysis and chromatin remodeler terms.
      supported_by:
        - reference_id: PMID:10811623
          supporting_text: Biochemical experiments using Chd1p purified from 
            yeast showed that it reconfigures the structure of nucleosome core 
            particles
  - term:
      id: GO:0030874
      label: nucleolar chromatin
    evidence_type: IDA
    original_reference_id: PMID:17259992
    review:
      summary: IDA evidence from ChIP studies shows CHD1 localizes to nucleolar 
        chromatin (rDNA regions). CHD1 directly functions at nucleolar sites in 
        rRNA gene transcription.
      action: ACCEPT
      reason: CHD1 localizes to and functions in nucleolar chromatin context. 
        This appropriately specific cellular component reflects CHD1's rDNA 
        association.
      supported_by:
        - reference_id: PMID:17259992
          supporting_text: RNA polymerase I in yeast transcribes dynamic 
            nucleosomal rDNA
  - term:
      id: GO:0031490
      label: chromatin DNA binding
    evidence_type: IDA
    original_reference_id: PMID:12682017
    review:
      summary: IDA evidence from localization studies demonstrates CHD1 binds 
        chromatin DNA specifically in context of nucleosomes. This is more 
        specific than generic DNA binding.
      action: ACCEPT
      reason: CHD1 binds DNA within chromatin context (not free DNA). This 
        appropriately specific term distinguishes chromatin-DNA from 
        unconstrained DNA binding.
      supported_by:
        - reference_id: PMID:12682017
          supporting_text: Chromatin remodeling protein Chd1 interacts with 
            transcription elongation factors and localizes to transcribed genes
  - term:
      id: GO:0046695
      label: SLIK (SAGA-like) complex
    evidence_type: IDA
    original_reference_id: PMID:15647753
    review:
      summary: IDA evidence confirms CHD1 is a component of SLIK complex 
        (related to SAGA). CHD1 functions in SLIK-mediated transcriptional 
        regulation and chromatin remodeling.
      action: ACCEPT
      reason: CHD1 is documented subunit of SLIK complex. This appropriately 
        specific cellular component annotation complements SAGA complex 
        annotation above.
      supported_by:
        - reference_id: PMID:15647753
          supporting_text: Chd1 chromodomain links histone H3 methylation with 
            SAGA- and SLIK-dependent acetylation
  - term:
      id: GO:0140002
      label: histone H3K4me3 reader activity
    evidence_type: IDA
    original_reference_id: PMID:15647753
    review:
      summary: IDA evidence demonstrates CHD1 chromodomain reads histone H3 
        methylation marks. CHD1 binds methylated histone H3 through conserved 
        chromodomain recognition motifs, enabling substrate specificity in SAGA 
        complex.
      action: ACCEPT
      reason: CHD1 has documented histone H3K4me3 reader activity through 
        chromodomain structure. However, yeast CHD1 may have lower specificity 
        than mammalian ortholog. Core signaling function linking histone marks 
        to remodeling activity.
      supported_by:
        - reference_id: PMID:15647753
          supporting_text: Chd1 chromodomain links histone H3 methylation with 
            SAGA- and SLIK-dependent acetylation
  - term:
      id: GO:2000104
      label: negative regulation of DNA-templated DNA replication
    evidence_type: IGI
    original_reference_id: PMID:18245327
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:18245327
          supporting_text: A role for Chd1 and Set2 in negatively regulating DNA
            replication in Saccharomyces cerevisiae
core_functions:
  - molecular_function:
      id: GO:0140658
      label: ATP-dependent chromatin remodeler activity
    description: CHD1's defining molecular function - catalyzes ATP-dependent 
      nucleosome repositioning and spacing through ATPase domain ratcheting 
      mechanism and linker DNA binding via SANT/SLIDE domains
references:
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
      Location vocabulary mapping
    findings: []
  - id: GO_REF:0000116
    title: Automatic Gene Ontology annotation based on Rhea mapping
    findings: []
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning
      models
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:10811623
    title: The chromo domain protein chd1p from budding yeast is an 
      ATP-dependent chromatin-modifying factor
    findings: []
  - id: PMID:12242279
    title: RNA polymerase II elongation factors of Saccharomyces cerevisiae - a 
      targeted proteomics approach
    findings: []
  - id: PMID:12504018
    title: A role for chromatin remodeling in transcriptional termination by RNA
      polymerase II
    findings: []
  - id: PMID:12682017
    title: Chromatin remodeling protein Chd1 interacts with transcription 
      elongation factors and localizes to transcribed genes
    findings: []
  - id: PMID:14576278
    title: The proteome of Saccharomyces cerevisiae mitochondria
    findings: []
  - id: PMID:14759368
    title: High-definition macromolecular composition of yeast RNA-processing 
      complexes
    findings: []
  - id: PMID:15647753
    title: Chd1 chromodomain links histone H3 methylation with SAGA- and 
      SLIK-dependent acetylation
    findings: []
  - id: PMID:16429126
    title: Proteome survey reveals modularity of the yeast cell machinery
    findings: []
  - id: PMID:16554755
    title: Global landscape of protein complexes in the yeast Saccharomyces 
      cerevisiae
    findings: []
  - id: PMID:16823961
    title: Toward the complete yeast mitochondrial proteome - multidimensional 
      separation techniques for mitochondrial proteomics
    findings: []
  - id: PMID:17259992
    title: RNA polymerase I in yeast transcribes dynamic nucleosomal rDNA
    findings: []
  - id: PMID:18245327
    title: A role for Chd1 and Set2 in negatively regulating DNA replication in 
      Saccharomyces cerevisiae
    findings: []
  - id: PMID:19536198
    title: An atlas of chaperone-protein interactions in Saccharomyces 
      cerevisiae - implications to protein folding pathways in the cell
    findings: []
  - id: PMID:19948887
    title: Histone H3K4 and K36 methylation, Chd1 and Rpd3S oppose the functions
      of Saccharomyces cerevisiae Spt4-Spt5 in transcription
    findings: []
  - id: PMID:20489023
    title: A global protein kinase and phosphatase interaction network in yeast
    findings: []
  - id: PMID:21179020
    title: Defining the budding yeast chromatin-associated interactome
    findings: []
  - id: PMID:21623345
    title: The DNA-binding domain of the Chd1 chromatin-remodelling enzyme 
      contains SANT and SLIDE domains
    findings: []
  - id: PMID:21940898
    title: A role for Snf2-related nucleosome-spacing enzymes in genome-wide 
      nucleosome organization
    findings: []
  - id: PMID:22922743
    title: Chromatin remodelers Isw1 and Chd1 maintain chromatin structure 
      during transcription by preventing histone exchange
    findings: []
  - id: PMID:23468649
    title: ISWI and CHD chromatin remodelers bind promoters but act in gene 
      bodies
    findings: []
  - id: PMID:25216679
    title: Architecture of the Saccharomyces cerevisiae SAGA transcription 
      coactivator complex
    findings: []
  - id: PMID:26861626
    title: The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set 
      nucleosome spacing in vivo
    findings: []
  - id: PMID:31222142
    title: The chromatin remodeler Chd1 regulates cohesin in budding yeast and 
      humans
    findings: []
  - id: PMID:33174727
    title: Yeast Chd1p Unwraps the Exit Side DNA upon ATP Binding to Facilitate 
      the Nucleosome Translocation Occurring upon ATP Hydrolysis
    findings: []
  - id: PMID:34520455
    title: The chromatin remodeler Chd1 supports MRX and Exo1 functions in 
      resection of DNA double-strand breaks
    findings: []
  - id: PMID:37968396
    title: The social and structural architecture of the yeast protein 
      interactome
    findings: []
  - id: file:yeast/CHD1/CHD1-deep-research-perplexity.md
    title: Deep research report on CHD1
    findings: []

CHD1

Gene Description