HDA1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: IBA propagated from a broad PAINT node: the GOA WITH/FROM field carries 19 gene-product donors spanning fly, mouse, rat and Arabidopsis alongside human class II HDAC orthologs (including P56524/HDAC4 and Q9UBN7/HDAC6), plus the ancestral node PANTHER:PTN000065904. Nucleocytoplasmic distribution is a conserved property of this HDAC subfamily, so the compartment call is a considered node placement, not an inference artifact. The GOA qualifier, however, is is_active_in rather than located_in, and that is where the annotation overshoots what the donor evidence supports for HDA1. Reason: The compartment itself is plausible and the IBA-overturn bar is not met, so the term is retained rather than removed: there is no HDA1-specific evidence of divergence from, or loss of, the ancestral shuttling capacity of this subfamily, and absence of a positive cytoplasmic localization study for HDA1 is not evidence against one. What is not established is the is_active_in qualifier, which asserts that HDA1 executes its molecular function in the cytoplasm, not merely that it can be present there. The cytoplasmic activity that anchors this node in the donors is HDAC6 alpha-tubulin deacetylation, executed by a class IIb-specific architecture (tandem catalytic domains plus a ZnF-UBP domain) that HDA1 does not possess, while class IIa shuttling is governed by 14-3-3-binding phosphosites that are likewise not an evident HDA1 feature. HDA1's only established molecular function -- histone deacetylation as the catalytic subunit of the nuclear HDA1 complex with HDA2 and HDA3 -- is chromatin-associated and therefore nuclear. The falcon deep-research synthesis independently judged the cytoplasm call weak or incorrect for HDA1 itself, noting that the cytosolic relocalization under hypoxia was reported for the partners HDA2/HDA3 rather than for HDA1. MARK_AS_OVER_ANNOTATED keeps the compartment while flagging the activity claim as unsupported; a located_in qualifier would be the accurate form of this annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN000065904 · PAINT ancestral node for the class II HDAC family SUPPORTS TRANSFER The node placement supports HDA1 being present in the cytoplasm; it does not establish that HDA1 executes a molecular function there, which is what the is_active_in qualifier asserts. UniProtKB:Q9UBN7 · human HDAC6 SUPPORTS SOURCE BUT NOT TARGET The strongest cytoplasmic-activity signal among the donors is HDAC6 alpha-tubulin deacetylation, which depends on a class IIb-specific architecture (tandem catalytic domains plus a ZnF-UBP domain) that HDA1 does not have. UniProtKB:P56524 · human HDAC4 SUPPORTS SOURCE BUT NOT TARGET Class IIa nucleocytoplasmic shuttling is regulated by 14-3-3-binding phosphosites that are not an evident HDA1 feature; shuttling in any case speaks to localization rather than to cytoplasmic catalysis. Supporting Evidence: file:yeast/HDA1/HDA1-goa.tsv FB:FBgn0026428\|FB:FBgn0041210\|MGI:MGI:1333752\|MGI:MGI:1333784\|MGI:MGI:3036234\|PANTHER:PTN000065904\|RGD:619979\|RGD:619980\|TAIR:locus:2095087\|TAIR:locus:2119201\|TAIR:locus:2159446\|TAIR:locus:2159461\|UniProtKB:D6XGM6\|UniProtKB:P56524\|UniProtKB:Q2QWU2\|UniProtKB:Q8WUI4\|UniProtKB:Q969S8\|UniProtKB:Q9UBN7\|UniProtKB:Q9UKV0\|UniProtKB:Q9UQL6 file:yeast/HDA1/HDA1-deep-research-falcon.md Cytoplasm (CC): likely weak/incorrect for Hda1 itself.
GO:0040029 epigenetic regulation of gene expression	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation through phylogenetic conservation of HDAC function in epigenetic regulation. Well-supported core function. Reason: HDA1 catalyzes histone deacetylation, a primary epigenetic modification mechanism. HDA1's role in regulating chromatin acetylation status directly controls gene expression through chromatin remodeling. This is a phylogenetically conserved function well-documented for Class II HDACs. The IBA annotation appropriately reflects HDA1's core biological role in epigenetic gene regulation. Supporting Evidence: PMID:11287668 is likely the catalytic subunit of the HDA1-containing complex that is involved in TUP1-specific repression and global deacetylation in yeast. PMID:19573535 2009 Jun 30. Structural and functional studies of the yeast class II Hda1 histone deacetylase complex. file:yeast/HDA1/HDA1-deep-research-falcon.md At PHO5 and adjacent ORFs, deletion of HDA1 increases acetylation across a multi-kb region, consistent with domain-wide chromatin regulation influencing basal transcriptional states.
GO:0000118 histone deacetylase complex	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation through phylogenetic conservation confirming HDA1 as structural component of HDAC complex. Reason: HDA1 is the catalytic core subunit of the yeast Class II HDA1 complex, which also includes non-catalytic subunits HDA2 and HDA3. The HDA1 complex is a well-characterized functional unit. IBA inference from HDAC complex orthologs appropriately identifies HDA1's complex assembly and localization. Supporting Evidence: PMID:8663039 HDA1 and HDA3 are components of a yeast histone deacetylase (HDA) complex PMID:11287668 HDA2 and HDA3 are related proteins that interact with and are essential for the activity of the yeast histone deacetylase HDA1 file:yeast/HDA1/HDA1-deep-research-falcon.md Hda1 functions in a multi-subunit histone deacetylase complex with Hda2 and Hda3, where Hda2/Hda3 are required for full Hda1 activity and targeting.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation based on UniProtKB Subcellular Location mapping. Correct, consistent with multiple experimental studies. Reason: HDA1 localizes to the nucleus where it functions in chromatin deacetylation and transcriptional repression. While based on automated mapping from UniProt keywords, this annotation is consistently supported by experimental evidence showing HDA1's nuclear localization and function in nuclear chromatin regulation. Supporting Evidence: GO_REF:0000044 Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping PMID:16415367 Suppressor analysis of a histone defect identifies a new function for the hda1 complex in chromosome segregation file:yeast/HDA1/HDA1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. file:yeast/HDA1/HDA1-deep-research-falcon.md ChIP-qPCR/ChIP-seq shows Hda1 occupancy at promoters and coding regions of highly transcribed genes, consistent with nuclear localization and chromatin association.
GO:0006325 chromatin organization	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation based on UniProtKB keyword mapping. Supported by HDA1's documented role in chromatin structure. Reason: HDA1's histone deacetylase activity directly affects chromatin organization through modification of histone acetylation status. Histone deacetylation promotes chromatin condensation and heterochromatin formation. This is an appropriate parent-level biological process annotation capturing HDA1's fundamental role in chromatin structure regulation. Supporting Evidence: PMID:19573535 2009 Jun 30. Structural and functional studies of the yeast class II Hda1 histone deacetylase complex. file:yeast/HDA1/HDA1-deep-research-falcon.md At PHO5 and adjacent ORFs, deletion of HDA1 increases acetylation across a multi-kb region, consistent with domain-wide chromatin regulation influencing basal transcriptional states.
GO:0006351 DNA-templated transcription	IEA GO_REF:0000043	MODIFY	Summary: IEA annotation based on UniProtKB keyword mapping. HDA1 does not directly catalyze transcription but modulates it through chromatin remodeling. Reason: HDA1 does not directly catalyze DNA-templated transcription. Rather, HDA1 modulates transcription by altering chromatin structure through histone deacetylation, typically resulting in transcriptional repression. A more accurate annotation would be negative regulation of transcription or regulation of transcription. The direct transcription process term is mechanistically inaccurate. Proposed replacements: negative regulation of transcription by RNA polymerase II regulation of DNA-templated transcription Supporting Evidence: PMID:11287668 HDA2 and HDA3 are related proteins that interact with and are essential for the activity of the yeast histone deacetylase HDA1. file:yeast/HDA1/HDA1-deep-research-falcon.md Tup1 recruits Hda1 for localized histone deacetylation and repression at ENA1 and other genes file:yeast/HDA1/HDA1-deep-research-falcon.md The dominant evidence supports repression/dampening via deacetylation.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000117	ACCEPT	Summary: IEA from ARBA machine learning model. Appropriate for HDA1's regulatory function in transcription. Reason: HDA1 regulates transcription through its deacetylase activity on chromatin. This parent-level process term appropriately captures HDA1's role in transcriptional control. While HDA1 typically functions as a transcriptional repressor, the broader "regulation of transcription" captures its functional role without overspecifying mechanism. Supporting Evidence: PMID:11287668 HDA2 and HDA3 are related proteins that interact with and are essential for the activity of the yeast histone deacetylase HDA1. file:yeast/HDA1/HDA1-deep-research-falcon.md Strong experimental evidence supports chromatin association, histone-tail deacetylation (H2B/H3 and context-dependent H4), and transcriptional repression.
GO:0010557 positive regulation of macromolecule biosynthetic process	IEA GO_REF:0000117	REMOVE	Summary: IEA annotation from ARBA. HDA1's primary documented role is transcriptional repression, not positive regulation. Reason: This annotation is mechanistically inconsistent with HDA1's documented function. HDA1 catalyzes histone deacetylation that typically promotes gene silencing and heterochromatin formation, resulting in negative regulation of transcription and suppression of biosynthetic processes. While HDA1 might positively regulate transcription at specific loci in particular cellular contexts, the predominant and well-characterized mechanism is transcriptional repression. The ARBA inference appears to contradict experimental evidence for HDA1's core function. Supporting Evidence: PMID:11287668 HDA2 and HDA3 are related proteins that interact with and are essential for the activity of the yeast histone deacetylase HDA1. PMID:11172717 TUP1 utilizes histone H3/H2B-specific HDA1 deacetylase to repress gene activity in yeast. file:yeast/HDA1/HDA1-deep-research-falcon.md The dominant evidence supports repression/dampening via deacetylation. file:yeast/HDA1/HDA1-deep-research-falcon.md Genome-wide data do note rare loci with paradoxical expression changes in hda1 mutants, but these are more consistent with indirect effects or pathway interactions than direct activation.
GO:0016787 hydrolase activity	IEA GO_REF:0000043	MODIFY	Summary: IEA annotation based on UniProtKB keyword hydrolase. Chemically true for HDACs, but too broad for HDA1 because specific histone deacetylase terms are available. Reason: HDA1 catalyzes hydrolytic deacetylation, so hydrolase is not wrong, but the term is too general to be informative for GO curation. The evidence supports the specific histone lysine deacetylase activity, especially the hydrolytic mechanism term GO:0141221, rather than a generic hydrolase parent. Proposed replacements: histone deacetylase activity, hydrolytic mechanism histone deacetylase activity Supporting Evidence: GO_REF:0000043 Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping file:yeast/HDA1/HDA1-deep-research-falcon.md Too broad; evidence is specific for histone lysine deacetylase/HDAC activity rather than generic hydrolase
GO:0141221 histone deacetylase activity, hydrolytic mechanism	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation from RHEA/EC number mapping. Precise molecular function annotation for HDA1. Reason: GO:0141221 is a more specific child term of histone deacetylase activity that explicitly specifies the hydrolytic deacetylation mechanism (as opposed to NAD-dependent deacetylation used by sirtuins). This correctly distinguishes HDA1 as a Class II zinc-dependent hydrolytic HDAC. The RHEA mapping to EC 3.5.1.98 is mechanistically accurate. This is the most informative molecular function annotation for HDA1's core enzymatic activity. Supporting Evidence: GO_REF:0000120 Combined Automated Annotation using Multiple IEA Methods with RHEA:58196 and EC:3.5.1.98 file:yeast/HDA1/HDA1-deep-research-falcon.md Structural/mechanistic analysis places Hda1 in the Zn2+-dependent Rpd3/Hda1 family; TSA-sensitive HDAC complex reconstituted
GO:0005515 protein binding	IPI PMID:11287668 HDA2 and HDA3 are related proteins that interact with and ar...	REMOVE	Summary: IPI annotation indicating interaction with Q06623 (HDA2). Generic protein binding term. Reason: Following curation guidelines, generic 'protein binding' terms should be replaced with more informative molecular function annotations that specify the functional consequence of the interaction. HDA1's interaction with HDA2 is documented in GO:0000118 (histone deacetylase complex) and GO:0070823 (HDA1 complex), which more precisely capture HDA1's role as a complex component. The protein binding annotation does not inform about what specific function this binding enables or supports. Supporting Evidence: PMID:11287668 HDA2 and HDA3 are related proteins that interact with and are essential for the activity of the yeast histone deacetylase HDA1 file:yeast/HDA1/HDA1-deep-research-falcon.md Some support for Hda1 self-interaction and partner binding, but broad GO terms are less informative than complex membership
GO:0005515 protein binding	IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine...	REMOVE	Summary: IPI annotation from proteome survey. Generic protein binding with unspecified partner. Reason: Generic protein binding annotation. The associated reference PMID:16429126 appears to be a proteome-wide interaction survey with unspecified interaction partners. Without specific functional relevance of the binding partner, this annotation provides minimal informational value. More specific molecular function terms already capture HDA1's functionally relevant protein interactions. Supporting Evidence: PMID:16429126 Proteome survey reveals modularity of the yeast cell machinery file:yeast/HDA1/HDA1-deep-research-falcon.md Some support for Hda1 self-interaction and partner binding, but broad GO terms are less informative than complex membership
GO:0005515 protein binding	IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom...	REMOVE	Summary: IPI annotation from global landscape of protein complexes. Generic binding annotation. Reason: Generic protein binding from high-throughput interaction data. This annotation lacks specificity regarding functional consequence of binding. HDA1's documented complex assembly and chromatin binding are captured more precisely by other annotations (GO:0003682 chromatin binding, GO:0070823 HDA1 complex). Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae file:yeast/HDA1/HDA1-deep-research-falcon.md Some support for Hda1 self-interaction and partner binding, but broad GO terms are less informative than complex membership
GO:0005515 protein binding	IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome.	REMOVE	Summary: IPI annotation from budding yeast chromatin-associated interactome study. Reason: Generic protein binding annotation without specification of interaction partner or functional relevance. HDA1's chromatin-associated function is more precisely captured by GO:0003682 (chromatin binding) annotation already present. This generic term provides redundant and less informative coverage. Supporting Evidence: PMID:21179020 Defining the budding yeast chromatin-associated interactome file:yeast/HDA1/HDA1-deep-research-falcon.md Some support for Hda1 self-interaction and partner binding, but broad GO terms are less informative than complex membership
GO:0005515 protein binding	IPI PMID:37968396 The social and structural architecture of the yeast protein ...	REMOVE	Summary: IPI annotation from social architecture of yeast interactome. Reason: Generic protein binding from large-scale interaction mapping. The annotation does not specify functional consequence or identify the interaction partner. Functionally relevant annotations (GO:0070823 HDA1 complex, GO:0003682 chromatin binding) more precisely capture HDA1's binding interactions. This generic annotation should be removed following best practices to avoid uninformative molecular function terms. Supporting Evidence: PMID:37968396 The social and structural architecture of the yeast protein interactome file:yeast/HDA1/HDA1-deep-research-falcon.md Some support for Hda1 self-interaction and partner binding, but broad GO terms are less informative than complex membership
GO:0042802 identical protein binding	IPI PMID:11287668 HDA2 and HDA3 are related proteins that interact with and ar...	KEEP AS NON CORE	Summary: IPI annotation indicating HDA1 homodimer formation or self-association. Reason: HDA1 can form homodimers or oligomers, but the predominant and functionally essential interaction is with HDA2/HDA3 subunits to form the catalytically active HDA1 complex. Homodimerization may represent a secondary or non-functional interaction. The annotation is likely correct but represents a non-core molecular interaction. The HDA1 complex assembly with heteromeric partners (GO:0070823) is the primary functional assembly. Supporting Evidence: PMID:11287668 HDA1 interacts with itself and with the HDA2-HDA3 subcomplex to form a likely tetramer. file:yeast/HDA1/HDA1-deep-research-falcon.md Some support for Hda1 self-interaction and partner binding, but broad GO terms are less informative than complex membership
GO:0042802 identical protein binding	IPI PMID:18719252 High-quality binary protein interaction map of the yeast int...	KEEP AS NON CORE	Summary: IPI annotation from high-quality binary protein interaction map. Reason: This annotation documents HDA1 self-association or homodimer formation detected in systematic yeast interactome mapping. While the interaction is likely genuine, homodimerization is not the predominant functional assembly compared to the essential HDA1-HDA2-HDA3 complex. This represents a secondary molecular interaction, not a core function. Supporting Evidence: PMID:18719252 High-quality binary protein interaction map of the yeast interactome network file:yeast/HDA1/HDA1-deep-research-falcon.md Some support for Hda1 self-interaction and partner binding, but broad GO terms are less informative than complex membership
GO:0042802 identical protein binding	IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome.	KEEP AS NON CORE	Summary: IPI annotation from chromatin-associated interactome study. Reason: HDA1 self-interaction documented in chromatin-associated protein interaction study. While potentially real, homodimerization is not characterized as essential or functionally distinct from the core HDA1 complex assembly with HDA2/HDA3. Mark as non-core peripheral interaction. Supporting Evidence: PMID:21179020 Defining the budding yeast chromatin-associated interactome file:yeast/HDA1/HDA1-deep-research-falcon.md Some support for Hda1 self-interaction and partner binding, but broad GO terms are less informative than complex membership
GO:0000122 negative regulation of transcription by RNA polymerase II	IDA PMID:11287668 HDA2 and HDA3 are related proteins that interact with and ar...	ACCEPT	Summary: IDA annotation documenting transcriptional repression function of HDA1. Reason: PMID:11287668 provides direct evidence that HDA1 mediates transcriptional repression through its deacetylase activity. HDA1's histone deacetylation promotes heterochromatin formation and represses transcription at target loci. This is a core biological process function well-supported by direct experimental evidence and represents one of HDA1's primary functional roles. Supporting Evidence: PMID:11287668 is likely the catalytic subunit of the HDA1-containing complex that is involved in TUP1-specific repression and global deacetylation in yeast. file:yeast/HDA1/HDA1-deep-research-falcon.md Tup1 recruits Hda1 for localized histone deacetylation and repression at ENA1 and other genes
GO:0008270 zinc ion binding	RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr...	KEEP AS NON CORE	Summary: RCA annotation from systematic zinc proteome study. HDA1 zinc binding is mechanistically important for the zinc-dependent HDAC fold but is not the core activity itself. Reason: Class II HDAC catalysis depends on zinc coordination, so the annotation is biochemically plausible and supported by zinc-proteome and HDAC-family evidence. However, zinc ion binding is an enabling cofactor interaction rather than HDA1's main evolved activity; the core function is hydrolytic histone deacetylase activity within chromatin-associated HDA1C. Supporting Evidence: PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc proteome. PMID:19573535 2009 Jun 30. Structural and functional studies of the yeast class II Hda1 histone deacetylase complex. file:yeast/HDA1/HDA1-deep-research-falcon.md Structural/mechanistic analysis places Hda1 in the Zn2+-dependent Rpd3/Hda1 family; TSA-sensitive HDAC complex reconstituted
GO:0000122 negative regulation of transcription by RNA polymerase II	IMP PMID:11172717 TUP1 utilizes histone H3/H2B-specific HDA1 deacetylase to re...	ACCEPT	Summary: IMP annotation from mutant phenotype study. HDA1 deletion/mutation results in derepression of normally silenced genes. Reason: PMID:11172717 provides direct evidence that HDA1 negatively regulates RNA Pol II transcription. Mutations affecting HDA1 result in transcriptional derepression at H3/H2B-specific loci, confirming HDA1's role as a transcriptional repressor. IMP evidence from mutant analysis is strong support for this biological process function. This is a core documented role for HDA1. Supporting Evidence: PMID:11172717 TUP1 utilizes histone H3/H2B-specific HDA1 deacetylase to repress gene activity in yeast file:yeast/HDA1/HDA1-deep-research-falcon.md Tup1 recruits Hda1 for localized histone deacetylation and repression at ENA1 and other genes
GO:0000122 negative regulation of transcription by RNA polymerase II	IMP PMID:17121596 H4 acetylation does not replace H3 acetylation in chromatin ...	UNDECIDED	Summary: IMP annotation from a study of histone acetylation during Adr1-dependent transcription activation; accessible abstract does not mention HDA1. Reason: The cached abstract for PMID:17121596 discusses Gcn5/Esa1-dependent histone acetylation changes during activation of Adr1-dependent genes, but it does not mention HDA1 or provide accessible evidence that an HDA1 perturbation causes derepression. Full text is not available in the cache, so this annotation should remain undecided rather than accepted as HDA1-specific negative regulation of RNA polymerase II transcription. Supporting Evidence: PMID:17121596 In cells lacking Gcn5 activity, the H3 acetylation increase does not occur and an unexpected increase of histone H4 acetylation is observed.
GO:0000122 negative regulation of transcription by RNA polymerase II	IGI PMID:17974563 A poised initiation complex is activated by SNF1.	ACCEPT	Summary: IGI annotation showing genetic interaction in transcriptional control. Reason: IGI annotation indicating genetic interaction at promoters where HDA1 and other factors coordinate transcriptional regulation. PMID:17974563 references a poised initiation complex activated by SNF1, with HDA1 functioning in coordination with other chromatin regulators. While less direct than IDA/IMP, IGI evidence supports HDA1's role in negative transcriptional regulation through pathway analysis. Supporting Evidence: PMID:17974563 A poised initiation complex is activated by SNF1 file:yeast/HDA1/HDA1-deep-research-falcon.md Tup1 recruits Hda1 for localized histone deacetylation and repression at ENA1 and other genes
GO:0003682 chromatin binding	IDA PMID:16415367 Suppressor analysis of a histone defect identifies a new fun...	ACCEPT	Summary: IDA annotation documenting direct chromatin association of HDA1. Reason: PMID:16415367 provides direct experimental evidence that HDA1 binds chromatin. The study identifying suppression of histone defects by the HDA1 complex demonstrates direct physical association between HDA1 and chromatin. This is a fundamental molecular function reflecting HDA1's mechanism - the complex must associate with chromatin to access histone substrates for deacetylation. Supporting Evidence: PMID:16415367 Jan 16. Suppressor analysis of a histone defect identifies a new function for the hda1 complex in chromosome segregation. PMID:19573535 2009 Jun 30. Structural and functional studies of the yeast class II Hda1 histone deacetylase complex. file:yeast/HDA1/HDA1-deep-research-falcon.md ChIP-qPCR/ChIP-seq shows Hda1 occupancy at promoters and coding regions of highly transcribed genes, consistent with nuclear localization and chromatin association. file:yeast/HDA1/HDA1-deep-research-falcon.md Hda1 functions in a multi-subunit histone deacetylase complex with Hda2 and Hda3, where Hda2/Hda3 are required for full Hda1 activity and targeting.
GO:0004407 histone deacetylase activity	IDA PMID:19573535 Structural and functional studies of the yeast class II Hda1...	ACCEPT	Summary: IDA annotation of core enzymatic activity from structural and functional characterization. Reason: PMID:19573535 provides structural and functional characterization of purified, recombinant HDA1 complex with direct enzymatic assays demonstrating histone deacetylase activity. This is the canonical molecular function of HDA1. IDA evidence from direct enzyme kinetics and structural determination is the highest quality evidence for this core activity. This annotation is central to HDA1's identity. Supporting Evidence: PMID:19573535 2009 Jun 30. Structural and functional studies of the yeast class II Hda1 histone deacetylase complex. file:yeast/HDA1/HDA1-deep-research-falcon.md Strong experimental evidence supports chromatin association, histone-tail deacetylation (H2B/H3 and context-dependent H4), and transcriptional repression. file:yeast/HDA1/HDA1-deep-research-falcon.md Tup1 recruits Hda1 to deacetylate histones H3 and H2B at promoter-adjacent nucleosomes (e.g., ENA1), supporting histone-substrate specificity and a repression mechanism. file:yeast/HDA1/HDA1-deep-research-falcon.md Modern spike-in normalized ChIP-seq/ChIP-qPCR demonstrates Hda1C-dependent H4 deacetylation within coding regions of highly transcribed genes.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:17706600 Regulation of the HAP1 gene involves positive actions of his...	KEEP AS NON CORE	Summary: IMP annotation suggesting HDA1 positively regulates some genes, contrasting with predominant repressive function. Reason: PMID:17706600 (Regulation of the HAP1 gene involves positive actions of histone deacetylases) documents a specific context where HDA1 contributes to positive transcriptional regulation of HAP1. While HDA1's primary and predominant function is transcriptional repression, specific genes may require deacetylation for activation in particular cellular contexts or through specific chromatin domains. This represents a context-specific, non-core function of HDA1. The predominant role as transcriptional repressor should be emphasized in core functions. Supporting Evidence: PMID:17706600 Regulation of the HAP1 gene involves positive actions of histone deacetylases file:yeast/HDA1/HDA1-deep-research-falcon.md Genome-wide data do note rare loci with paradoxical expression changes in hda1 mutants, but these are more consistent with indirect effects or pathway interactions than direct activation. file:yeast/HDA1/HDA1-deep-research-falcon.md The dominant evidence supports repression/dampening via deacetylation.
GO:0070823 HDA1 complex	IDA PMID:11287668 HDA2 and HDA3 are related proteins that interact with and ar...	ACCEPT	Summary: IDA annotation documenting HDA1 as component of defined HDA1 complex. Reason: PMID:11287668 provides direct experimental evidence that HDA1 associates with HDA2 and HDA3 to form the functionally essential HDA1 complex. This is a well-characterized macromolecular assembly with defined composition (HDA1 catalytic subunit + HDA2/HDA3 structural subunits). This annotation correctly identifies HDA1's complex membership and is supported by multiple independent studies establishing this assembly. Supporting Evidence: PMID:11287668 HDA2 and HDA3 are related proteins that interact with and are essential for the activity of the yeast histone deacetylase HDA1 file:yeast/HDA1/HDA1-deep-research-falcon.md Hda2 and Hda3 physically interact with Hda1 and are essential for Hda1 deacetylase activity; disruption of any subunit disrupts activity in vitro and in vivo.
GO:0070823 HDA1 complex	IPI PMID:11287668 HDA2 and HDA3 are related proteins that interact with and ar...	ACCEPT	Summary: IPI annotation documenting HDA2 as interaction partner in HDA1 complex assembly. Reason: IPI annotation specifying HDA2 (SGD:S000006383) as direct interaction partner. This is redundant with but complementary to other HDA1 complex annotations - it specifically documents the HDA1-HDA2 interaction. Both IDA and IPI evidence types support HDA1 complex assembly. The redundancy strengthens confidence in this essential functional assembly. Supporting Evidence: PMID:11287668 HDA2 and HDA3 are related proteins that interact with and are essential for the activity of the yeast histone deacetylase HDA1. file:yeast/HDA1/HDA1-deep-research-falcon.md Hda2 and Hda3 physically interact with Hda1 and are essential for Hda1 deacetylase activity; disruption of any subunit disrupts activity in vitro and in vivo.
GO:0070823 HDA1 complex	IDA PMID:8663039 HDA1 and HDA3 are components of a yeast histone deacetylase ...	ACCEPT	Summary: IDA annotation from early characterization of HDA1 complex components. Reason: PMID:8663039 is an early study demonstrating that HDA1 and HDA3 are components of a yeast histone deacetylase complex. This provides independent confirmation of HDA1 complex assembly from different experimental approach and timeframe. Multiple evidence sources for the same annotation (IDA from different studies) strengthen confidence in HDA1's role as a complex component. Supporting Evidence: PMID:8663039 HDA1 and HDA3 are components of a yeast histone deacetylase (HDA) complex file:yeast/HDA1/HDA1-deep-research-falcon.md Hda2 and Hda3 physically interact with Hda1 and are essential for Hda1 deacetylase activity; disruption of any subunit disrupts activity in vitro and in vivo.
GO:0070823 HDA1 complex	IDA PMID:8962081 HDA1 and RPD3 are members of distinct yeast histone deacetyl...	ACCEPT	Summary: IDA annotation documenting functional distinctness of HDA1 complex from RPD3 complex. Reason: PMID:8962081 demonstrates that HDA1 and RPD3 are members of distinct, functionally separate histone deacetylase complexes. This further supports HDA1 as a defined complex component and establishes its functional specialization. Multiple independent studies (PMID:8663039, PMID:11287668, PMID:8962081) consistently demonstrate HDA1's core role in the HDA1 complex assembly. Supporting Evidence: PMID:8962081 HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription file:yeast/HDA1/HDA1-deep-research-falcon.md Hda2 and Hda3 physically interact with Hda1 and are essential for Hda1 deacetylase activity; disruption of any subunit disrupts activity in vitro and in vivo.

Gene Description

Existing Annotations Review

Core Functions

Class II zinc-dependent hydrolytic histone deacetylase activity by Hda1 as the catalytic subunit of HDA1C, deacetylating histone lysines on chromatin including H3/H2B promoter contexts and H4 in highly transcribed gene bodies.

Chromatin association by Hda1/HDA1C that positions the deacetylase complex at promoters, coding regions, and broader chromatin domains for histone-tail deacetylation.

References

Suggested Questions for Experts

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Notes

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