RCO1

Existing Annotations Review

Gene Description

Existing Annotations Review

Core Functions

Organizes Rpd3S complex architecture by forming a homodimer and SID-MRG contacts with Eaf3, allowing assembly of two Eaf3-Rco1 modules around catalytic Rpd3/Sin3 and productive engagement of Rpd3S with nucleosomes in transcribed gene bodies.

References

Deep Research

Falcon

Perplexity

SGD

SGD gene description for RCO1 (yeast)

📚 Additional Documentation

Notes

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GO Term	Evidence	Action	Reason
GO:0006357 regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: The PANTHER IBA annotation to regulation of transcription by RNA polymerase II traces to the current PTN001236278 IBD in the Rco1 family. The term is broad, but sound: Rco1 is the Rpd3S-specific chromatin reader/scaffold subunit that helps the complex maintain coding-region histone hypoacetylation and suppress cryptic intragenic and antisense initiation during Pol II transcription. Reason: The inherited process is consistent with the direct budding-yeast evidence used to seed PTN001236278. Although RCO1 does not bind DNA as a sequence-specific transcription factor or modify Pol II directly, GO:0006357 covers modulation of transcription by RNA polymerase II; Rco1 executes that process as part of Rpd3S by recognizing/positioning H3K36me-marked coding-region chromatin for Rpd3-dependent deacetylation. Negative regulation of antisense RNA transcription and the proposed chromatin organization row below capture more specific facets, so the broad parent is sound but non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN001236278 SUPPORTS TRANSFER Current PTHR47636 IBD for the fungal Rco1-family role in Pol II transcriptional regulation through Rpd3S; RCO1 is inside the annotated clade and has direct yeast support. Supporting Evidence: file:yeast/RCO1/RCO1-deep-research-perplexity.md The primary biological function of the Rpd3S complex, which depends critically on proper Rco1 function, is to suppress the initiation of cryptic transcripts that would otherwise initiate from internal promoters within the bodies of actively transcribed genes file:yeast/RCO1/RCO1-deep-research-falcon.md Rpd3S is a histone deacetylase complex that operates co-transcriptionally across coding regions (ORFs/gene bodies) to remove histone acetylation “in the wake” of RNA polymerase II (Pol II), thereby suppressing cryptic (spurious intragenic) transcription initiation. Rco1 is one of the Rpd3S-specific subunits underlying this gene-body surveillance function.
GO:0032221 Rpd3S complex	IBA GO_REF:0000033	ACCEPT	Summary: RCO1 is a core component of the Rpd3S histone deacetylase complex. UniProt explicitly states that RCO1 is a "Component of the RPD3C(S) complex composed of at least EAF3, RCO1, RPD3, SIN3, and UME1". RCO1 exists as a homodimer within this complex and is essential for Rpd3S assembly and function. This is one of the most precisely annotated functions. Reason: Excellent annotation. RCO1 is directly identified as a structural component of the Rpd3S complex (CPX-1851) through both direct experimental evidence (IDA annotations from PMID:16286007 and PMID:16286008) and phylogenetic inference (IBA). This is a core, defining function of RCO1. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001236278 SUPPORTS TRANSFER Current PTHR47636 IBD for Rpd3S-complex membership in fungal Rco1 homologs; the budding-yeast Rco1 protein and both PomBase descendants support complex membership. Supporting Evidence: file:yeast/RCO1/RCO1-uniprot.txt Component of the RPD3C(S) complex composed of at least EAF3, RCO1, RPD3, SIN3, and UME1. [ECO:0000269\|PubMed:16286008] file:yeast/RCO1/RCO1-deep-research-perplexity.md RCO1 is a 684-amino acid transcriptional regulatory protein in the model organism Saccharomyces cerevisiae that functions as an essential subunit of the Rpd3S histone deacetylase (HDAC) complex file:yeast/RCO1/RCO1-deep-research-falcon.md Rpd3S is classically described as a five-subunit complex (Rpd3, Sin3, Ume1, Eaf3, Rco1). Mechanistic work shows Rco1 is a critical interaction hub: Rco1 forms key contacts with Eaf3 (via a Sin3 interaction domain/SID interacting with Eaf3’s MRG domain) and is required for full Rpd3S nucleosome engagement and cryptic transcription suppression.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: RCO1 is a nuclear protein. The UniProt record explicitly states "SUBCELLULAR LOCATION: Nucleus {ECO:0000269\|PubMed:14562095}". This is a well-established subcellular localization supported by large-scale proteomics analysis. Reason: This is a correct and unambiguous annotation. RCO1 functions exclusively in the nucleus as part of the Rpd3S complex. The IEA evidence from UniProtKB subcellular location mapping is appropriate and is backed by experimental evidence (HDA from PMID:14562095 and NAS from PMID:9512514). Supporting Evidence: PMID:14562095 Global analysis of protein localization in budding yeast
GO:0006325 chromatin organization	IEA GO_REF:0000043	ACCEPT	Summary: RCO1 is involved in chromatin organization as a core component of the Rpd3S histone deacetylase complex. The complex deacetylates histones in gene bodies and works with linker histone Hho1 to maintain chromatin compaction and prevent nucleosome eviction. This is appropriately classified as a chromatin organization function. Reason: This annotation is correct. RCO1's primary role is chromatin organization through nucleosome deacetylation and cryptic transcription suppression. The IEA mapping from UniProtKB keywords is appropriate. Supporting evidence includes both the structural role in Rpd3S and the functional requirement for maintaining proper chromatin state in gene bodies. Supporting Evidence: file:yeast/RCO1/RCO1-deep-research-perplexity.md Cryo-EM structures of Rpd3S bound to nucleosome core particles have revealed multiple distinct functional states of the complex that shed light on how it achieves efficient deacetylation while also reorganizing chromatin structure file:yeast/RCO1/RCO1-deep-research-falcon.md Rpd3S is a histone deacetylase complex that operates co-transcriptionally across coding regions (ORFs/gene bodies) to remove histone acetylation “in the wake” of RNA polymerase II (Pol II), thereby suppressing cryptic (spurious intragenic) transcription initiation. Rco1 is one of the Rpd3S-specific subunits underlying this gene-body surveillance function.
GO:0006351 DNA-templated transcription	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: RCO1 indirectly influences DNA-templated transcription by maintaining proper chromatin structure and suppressing cryptic transcription initiation within gene bodies. However, this is an indirect effect mediated through chromatin modification rather than direct participation in the transcription machinery. The annotation is too general. Reason: RCO1 influences Pol-II transcription through its Rpd3S chromatin regulatory functions, but this UniProt keyword mapping to DNA-templated transcription is a broad process assertion that does not distinguish chromatin restoration from the core transcription machinery. Negative regulation of antisense RNA transcription and the proposed chromatin organization row are more informative Rpd3S terms. Supporting Evidence: file:yeast/RCO1/RCO1-deep-research-perplexity.md The mechanism by which this suppression occurs involves the coordinated action of Set2 methylation and Rpd3S deacetylation to maintain a hypoacetylated chromatin state over gene bodies
GO:0008270 zinc ion binding	IEA GO_REF:0000043	ACCEPT	Summary: RCO1 contains two PHD (plant homeobox) zinc finger domains (residues 260-309 and 414-472) that coordinate zinc ions as structural cofactors. The UniProt record explicitly identifies these ZN_FING features with PHD-type zinc fingers. Zinc binding is essential for the structural integrity and function of the PHD domains. Reason: This annotation is correct. RCO1 contains two PHD zinc finger motifs that require coordinated zinc ions for proper folding and function. The IEA evidence from UniProtKB keyword mapping is appropriate. Zinc ion binding is a structural requirement for RCO1's histone mark recognition capability. This is well-supported by the protein domain annotations and structural studies showing the importance of the PHD zinc fingers in nucleosome binding. Supporting Evidence: file:yeast/RCO1/RCO1-uniprot.txt ZN_FING 260..309 /note="PHD-type 1" and ZN_FING 414..472 /note="PHD-type 2" file:yeast/RCO1/RCO1-deep-research-perplexity.md RCO1 contains several critical domains including a plant homeobox (PHD) domain and a Sin3-interacting domain (SID), which together orchestrate the recognition of nucleosomes methylated at histone H3 lysine 36 file:yeast/RCO1/RCO1-deep-research-falcon.md Rco1 contains two plant homeodomain (PHD) zinc-finger modules (PHD1 and PHD2). Biochemical evidence indicates that both PHD1 and PHD2 bind the extreme N-terminus of histone H3 (H3 1–20) and that H3K4 trimethylation reduces binding—a mechanism that helps restrict Rpd3S away from promoter nucleosomes enriched in H3K4me3.
GO:0046872 metal ion binding	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: RCO1 contains metal-binding zinc finger domains, making metal ion binding a valid annotation. However, the more specific zinc ion binding (GO:0008270) is already annotated and is more informative. Reason: This is technically correct but overly general. RCO1 does bind metal ions (specifically zinc), but the more specific and informative annotation GO:0008270 (zinc ion binding) is already present. The broader metal ion binding term should be marked as non-core since zinc ion binding is the specific and functionally important metal-binding activity. This is a parent term that is less informative than the specific zinc annotation. Supporting Evidence: file:yeast/RCO1/RCO1-uniprot.txt Metal-binding; Zinc-finger keywords; ZN_FING features indicating zinc coordination
GO:0005515 protein binding	IPI PMID:15766533 Navigating the chaperone network: an integrative map of phys...	REMOVE	Summary: RCO1 interacts with multiple protein partners including Hsp90 chaperone, Rpd3, Sin3, Ume1, Eaf3, and other complex members. Multiple IPI annotations from co-immunoprecipitation studies demonstrate protein-protein interactions. However, "protein binding" is an uninformative molecular function term that does not describe the specific binding interactions or their biological significance. The specific interaction partners and complexes are already captured by other annotations (Rpd3S complex membership). Reason: While RCO1 does bind proteins (as documented by multiple IPI studies from PMIDs 15766533, 16429126, 16554755, 17101441, 19536198, 21179020, 23878396, 24843044, and 37968396), the term "protein binding" is too generic and uninformative. It does not distinguish between interaction partners or provide functional context. The specific interactions that matter most - with Rpd3S complex subunits Rpd3, Sin3, Ume1, and Eaf3 - are already captured by the "part_of: Rpd3S complex" annotation, while the high-throughput chaperone and interactome rows do not establish a more specific molecular-function term for Rco1. Removal only rejects the bare GO:0005515 assertion as uninformative. Supporting Evidence: PMID:15766533 Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperone PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae file:yeast/RCO1/RCO1-deep-research-perplexity.md Rco1 functions as a critical interaction hub that coordinates multiple layers of complex assembly and function
GO:0005515 protein binding	IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine...	REMOVE	Summary: Multiple IPI annotations document RCO1 protein binding interactions from proteome-wide studies. Reason: Generic "protein binding" is not informative as a molecular-function annotation for Rco1. This high-throughput complex-membership paper supports physical association, but not a more specific molecular-function replacement for the bare GO:0005515 row. Supporting Evidence: PMID:16429126 Proteome survey reveals modularity of the yeast cell machinery
GO:0005515 protein binding	IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom...	REMOVE	Summary: Multiple IPI annotations document RCO1 protein binding interactions from proteome-wide studies. Reason: Generic "protein binding" is not informative as a molecular-function annotation for Rco1. This high-throughput complex-mapping paper supports physical association, but not a more specific molecular-function replacement for the bare GO:0005515 row. Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae
GO:0005515 protein binding	IPI PMID:17101441 Analyzing chromatin remodeling complexes using shotgun prote...	REMOVE	Summary: Multiple IPI annotations document RCO1 protein binding interactions from proteome-wide studies. Reason: Generic "protein binding" is not informative as a molecular-function annotation for Rco1. The normalized spectral-counting reanalysis concerns Rpd3/Sin3 complex composition rather than a specific molecular function that would replace the bare GO:0005515 row. Supporting Evidence: PMID:17101441 Analyzing chromatin remodeling complexes using shotgun proteomics
GO:0005515 protein binding	IPI PMID:19536198 An atlas of chaperone-protein interactions in Saccharomyces ...	REMOVE	Summary: Multiple IPI annotations document RCO1 protein binding interactions from proteome-wide studies. Reason: Generic "protein binding" is not informative as a molecular-function annotation for Rco1. This chaperone-interaction atlas supports physical association, but not a more specific molecular-function replacement for the bare GO:0005515 row. Supporting Evidence: PMID:19536198 An atlas of chaperone-protein interactions in Saccharomyces cerevisiae
GO:0005515 protein binding	IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome.	REMOVE	Summary: Multiple IPI annotations document RCO1 protein binding interactions from proteome-wide studies. Reason: Generic "protein binding" is not informative as a molecular-function annotation for Rco1. This chromatin-associated interactome paper supports physical association, but not a more specific molecular-function replacement for the bare GO:0005515 row. Supporting Evidence: PMID:21179020 Defining the budding yeast chromatin-associated interactome
GO:0005515 protein binding	IPI PMID:23878396 The yeast Snt2 protein coordinates the transcriptional respo...	REMOVE	Summary: Multiple IPI annotations document RCO1 protein binding interactions from proteome-wide studies. Reason: Generic "protein binding" is not informative as a molecular-function annotation for Rco1. This Snt2 study does not establish a specific Rco1 molecular function that would replace the bare GO:0005515 row. Supporting Evidence: PMID:23878396 The yeast Snt2 protein coordinates the transcriptional response to hydrogen peroxide-mediated oxidative stress
GO:0005515 protein binding	IPI PMID:24843044 Eaf5/7/3 form a functionally independent NuA4 submodule link...	REMOVE	Summary: Multiple IPI annotations document RCO1 protein binding interactions from proteome-wide studies. Reason: Generic "protein binding" is not informative as a molecular-function annotation for Rco1. The Eaf3 interaction is compatible with Rpd3S biology, but the cited NuA4 submodule study does not establish a more specific Rco1 molecular-function replacement for the bare GO:0005515 row. Supporting Evidence: PMID:24843044 Eaf5/7/3 form a functionally independent NuA4 submodule linked to RNA polymerase II-coupled nucleosome recycling
GO:0005515 protein binding	IPI PMID:37968396 The social and structural architecture of the yeast protein ...	REMOVE	Summary: Multiple IPI annotations document RCO1 protein binding interactions from proteome-wide studies. Reason: Generic "protein binding" is not informative as a molecular-function annotation for Rco1. This 2023 interactome paper supports physical association, but not a more specific molecular-function replacement for the bare GO:0005515 row. Supporting Evidence: PMID:37968396 The social and structural architecture of the yeast protein interactome
GO:0000122 negative regulation of transcription by RNA polymerase II	NAS PMID:9512514 Histone deacetylase activity of Rpd3 is important for transc...	KEEP AS NON CORE	Summary: RCO1 is part of the Rpd3S complex, which suppresses cryptic transcription initiation within gene bodies. This represents negative regulation of transcription at internal promoters. However, the evidence is NAS (derived from ComplexPortal annotation), indicating this is a statement from the literature without direct experimental evidence in the cited paper. Reason: The annotation is mechanistically correct - Rpd3S does negatively regulate transcription by suppressing cryptic initiation. However, RCO1's specific role is in H3K4me0 / unmodified-H3 recognition (via its PHD fingers) and complex assembly, not direct transcription regulation (recognition of H3K36me3 is contributed by the Eaf3 chromodomain). The negative regulation is a consequence of chromatin organization. The more specific and core function is "negative regulation of antisense RNA transcription" (GO:0060195), which better captures RCO1's role in maintaining promoter directionality. This broader annotation should be marked non-core. Supporting Evidence: PMID:9512514 Histone deacetylase activity of Rpd3 is important for transcriptional repression in vivo file:yeast/RCO1/RCO1-deep-research-falcon.md Rpd3S is a histone deacetylase complex that operates co-transcriptionally across coding regions (ORFs/gene bodies) to remove histone acetylation “in the wake” of RNA polymerase II (Pol II), thereby suppressing cryptic (spurious intragenic) transcription initiation. Rco1 is one of the Rpd3S-specific subunits underlying this gene-body surveillance function.
GO:0005634 nucleus	NAS PMID:9512514 Histone deacetylase activity of Rpd3 is important for transc...	ACCEPT	Summary: This is a duplicate nucleus annotation from NAS evidence (literature statement). The HDA annotation from PMID:14562095 is more direct. Reason: Correct annotation. RCO1 is a nuclear protein. This NAS entry documents nucleus localization from literature. While the HDA annotation from PMID:14562095 is more direct, both are correct. Supporting Evidence: PMID:9512514 Histone deacetylase activity of Rpd3 is important for transcriptional repression in vivo
GO:0006334 nucleosome assembly	NAS PMID:22177115 The Rpd3 core complex is a chromatin stabilization module.	MARK AS OVER ANNOTATED	Summary: The Rpd3 core complex is described as a "chromatin stabilization module" that maintains nucleosome integrity and prevents nucleosome eviction. This could be interpreted as related to nucleosome assembly, though it is more accurately described as nucleosome maintenance and stabilization. Reason: RCO1's role is chromatin stabilization and nucleosome maintenance, not nucleosome assembly per se. The term "nucleosome assembly" typically refers to the assembly of nucleosome core particles from histone proteins and DNA, which is not RCO1's primary function. RCO1 maintains existing nucleosomes and prevents their disruption during transcription. The proposed chromatin organization row captures that Rpd3S function more directly than nucleosome assembly. Supporting Evidence: PMID:22177115 The Rpd3 core complex is a chromatin stabilization module
GO:0008270 zinc ion binding	RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr...	ACCEPT	Summary: This is a second annotation for zinc ion binding, now with RCA (inferred from Reviewed Computational Analysis) evidence from SGD, citing a paper on the cellular economy of the S. cerevisiae zinc proteome. This complements the IEA zinc-binding annotation from UniProt keyword mapping. Reason: RCO1 contains two PHD zinc finger domains that require zinc coordination, and UniProt records both ZN_FING PHD-type features. The reviewed computational analysis supports the same structural zinc ion binding assignment as the UniProt keyword row. Supporting Evidence: PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc proteome
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:24358376 The roles of the catalytic and noncatalytic activities of Rp...	KEEP AS NON CORE	Summary: RCO1 is required for maintaining transcription of many genes by suppressing cryptic transcription and maintaining productive transcription elongation. Deletion of rco1 causes reduction in expression of many genes and activation of cryptic transcripts. This could be viewed as RCO1 positively regulating transcription of main promoter transcripts. Reason: This IMP annotation is well-supported for the condition-specific Rpd3S activation of meiosis-specific genes such as IME1 and IME2, but it is not the defining coding-region function of Rco1. It is retained as non-core, while RCO1's direct reader/scaffold activity in Rpd3S and the suppression of cryptic intragenic and antisense transcription remain the central functions. Supporting Evidence: PMID:24358376 Specifically, the catalytic activity of Rpd3S activates the transcription of the two major positive regulators of meiosis, IME1 and IME2, under all growth conditions and activates the transcription of NDT80 only during vegetative growth.
GO:0005634 nucleus	HDA PMID:14562095 Global analysis of protein localization in budding yeast.	ACCEPT	Summary: RCO1 is a nuclear protein, determined by large-scale proteomics analysis of protein localization. This HDA annotation represents direct experimental evidence of nuclear localization. Within the nucleus, Rco1 is predominantly chromatin-associated and localized to active ORFs/gene bodies. Reason: Excellent annotation. HDA evidence from PMID:14562095 (large-scale protein localization analysis) directly documents RCO1's nuclear localization. This is one of the foundational observations about RCO1. Falcon deep research further specifies that within the nucleus Rco1 is predominantly in the chromatin fraction at active gene bodies, consistent with its co-transcriptional Rpd3S role. Supporting Evidence: PMID:14562095 Global analysis of protein localization in budding yeast file:yeast/RCO1/RCO1-deep-research-falcon.md Rco1 is predominantly chromatin-associated and localizes to active ORFs / gene bodies rather than promoters, consistent with Rpd3S function in transcribed coding regions. Fractionation studies place wild-type Rco1 mainly in the chromatin fraction.
GO:0000118 histone deacetylase complex	IDA PMID:16286008 Cotranscriptional set2 methylation of histone H3 lysine 36 r...	ACCEPT	Summary: RCO1 is an identified component of the histone deacetylase complex through direct experimental evidence (immunoprecipitation and mass spectrometry). This directly identifies RCO1 as part of a HDAC complex, which is the broader complex category. Reason: Excellent IDA annotation. RCO1 was directly identified as a component of the histone deacetylase complex through the landmark Keogh et al. (2005) paper that characterized the Rpd3S complex composition. This is a core structural annotation. The paper demonstrates RCO1's direct role in the Rpd3 histone deacetylase complex. Supporting Evidence: PMID:16286008 Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex file:yeast/RCO1/RCO1-deep-research-falcon.md RCO1 encodes Rco1, a non-catalytic chromatin regulatory protein. It is not itself a histone deacetylase; rather, it is a reader/targeting and regulatory subunit required for proper activity and chromatin engagement of the Rpd3S (Rpd3 small) HDAC complex.
GO:0006368 transcription elongation by RNA polymerase II	IGI PMID:19948887 Histone H3K4 and K36 methylation, Chd1 and Rpd3S oppose the ...	KEEP AS NON CORE	Summary: RCO1 participates in transcription elongation through its role in chromatin organization and preventing transcription disruption during elongation. The IGI evidence shows genetic interaction with Spt4-Spt5 factors that regulate elongation. However, RCO1's role is indirect - through chromatin modification rather than direct elongation machinery interaction. Reason: RCO1 supports transcription elongation indirectly by maintaining proper chromatin structure and preventing nucleosome disruption during polymerase transit. However, its primary function is not elongation per se, but rather preventing cryptic transcription through chromatin organization. The "positive regulation of transcription by RNA polymerase II" annotation better captures RCO1's more direct role. This elongation annotation should be marked non-core as it represents an indirect consequence of RCO1's chromatin regulatory function. Supporting Evidence: PMID:19948887 Histone H3K4 and K36 methylation, Chd1 and Rpd3S oppose the functions of Saccharomyces cerevisiae Spt4-Spt5 in transcription
GO:0030174 regulation of DNA-templated DNA replication initiation	IMP PMID:19417103 Genome-wide replication profiles indicate an expansive role ...	KEEP AS NON CORE	Summary: RCO1 (as part of Rpd3S) affects DNA replication timing and initiation frequency through chromatin regulation. The paper "Genome-wide replication profiles indicate an expansive role for Rpd3L in regulating replication initiation timing or efficiency" shows Rpd3L and Rpd3S influence replication through chromatin state. However, this is an indirect effect mediated through chromatin organization, not direct replication machinery interaction. Reason: RCO1 influences DNA replication timing indirectly through its role in chromatin organization and gene expression regulation. This is not a core function of RCO1. The primary function is cryptic transcription suppression and chromatin organization during transcription. Replication effects are pleiotropic consequences of altered chromatin state. This annotation should be marked non-core. Supporting Evidence: PMID:19417103 Genome-wide replication profiles indicate an expansive role for Rpd3L in regulating replication initiation timing or efficiency
GO:0006325 chromatin organization	IMP PMID:16286007 Histone H3 methylation by Set2 directs deacetylation of codi...	NEW	Summary: Proposed new annotation preserving RCO1's live chromatin-organization coverage after the older UniProt keyword-derived GO:0006325 row left current GOA. Rco1 is a core Rpd3S subunit required for coding-region histone deacetylation and suppression of spurious intragenic transcription. Reason: Rco1-specific Rpd3S evidence establishes that rco1 mutants accumulate excess histone acetylation across coding regions and initiate aberrant intragenic transcripts, while later genome-scale data independently support Rpd3S as an Eaf3/Rco1-dependent gene-body deacetylase that maintains chromatin homeostasis at highly expressed genes. The broad but direct GO:0006325 process term therefore remains justified even though the former UniProt keyword IEA has retired from GOA. Supporting Evidence: PMID:16286007 Mutants of RCO1 and EAF3 exhibited increased acetylation in the FLO8 and STE11 open reading frames (ORFs) and the appearance of aberrant transcripts initiating within the body of these ORFs. PMID:42418323 In parallel with the promoter-directed functions of Rpd3L, the Rpd3S complex contributes to global chromatin homeostasis by deacetylating the gene bodies of highly expressed genes.
GO:0032221 Rpd3S complex	IDA PMID:16286007 Histone H3 methylation by Set2 directs deacetylation of codi...	ACCEPT	Summary: RCO1 is directly identified as a component of the Rpd3S complex through co-immunoprecipitation and mass spectrometry. Two separate papers (PMID:16286007 and PMID:16286008) both identify RCO1 in Rpd3S, representing independent confirmation. Reason: Excellent IDA annotation. RCO1 is directly identified as a core component of Rpd3S in the landmark papers describing the complex composition. This is a foundational structural and functional annotation. Both PMID:16286007 and PMID:16286008 provide direct experimental evidence (IP-MS). Supporting Evidence: PMID:16286007 Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription
GO:0032221 Rpd3S complex	IDA PMID:16286008 Cotranscriptional set2 methylation of histone H3 lysine 36 r...	ACCEPT	Summary: RCO1 is directly identified as a component of the Rpd3S complex through co-immunoprecipitation. This is a second IDA annotation from independent confirmation in PMID:16286008. Reason: Excellent IDA annotation from a second independent source. Duplicate annotations with different PMIDs represent important independent confirmation of RCO1's role as a core Rpd3S component. Supporting Evidence: PMID:16286008 Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex
GO:0060195 negative regulation of antisense RNA transcription	IMP PMID:21248844 Nascent transcript sequencing visualizes transcription at nu...	ACCEPT	Summary: RCO1 deletion increases antisense transcription from promoters positioned opposite the 3' ends of genes. This represents RCO1's role in maintaining promoter directionality and preventing spurious antisense transcription initiation. This is one of RCO1's most important and specific functions. Reason: Excellent IMP annotation capturing one of RCO1's most important and specific functions. Nascent transcript sequencing clearly shows that rco1 deletion causes derepression of antisense transcription at 3' gene ends, indicating RCO1 enforces transcriptional directionality through chromatin modification. This is more specific and mechanistically informative than broader "negative regulation of transcription" terms. This is a CORE function of RCO1. Supporting Evidence: PMID:21248844 Nascent transcript sequencing visualizes transcription at nucleotide resolution file:yeast/RCO1/RCO1-deep-research-perplexity.md deletion of rco1 increases antisense transcription originating from antisense promoters positioned opposite the 3' ends of genes
GO:0032221 Rpd3S complex	IPI PMID:17101441 Analyzing chromatin remodeling complexes using shotgun prote...	ACCEPT	Summary: ComplexPortal now carries an additional RCO1 part_of Rpd3S complex row using IPI evidence from the normalized spectral-abundance reanalysis of Rpd3/Sin3 small and large histone deacetylase complexes. This is a duplicate confirmation of Rco1's core Rpd3S membership, which is already directly supported by IDA rows from the two 2005 Rpd3S discovery papers. Reason: Rco1 is an Rpd3S-specific subunit identified by MudPIT/IP-MS in the original Carrozza and Keogh Cell papers, and Florens et al. explicitly reanalyzed those Rpd3/Sin3 small and large histone deacetylase complex data using normalized spectral-abundance factors. The new ComplexPortal IPI row is therefore correct, but redundant with the more direct IDA rows for GO:0032221. Supporting Evidence: PMID:17101441 In this method review, we describe a reanalysis of the Rpd3/Sin3 small and large histone deacetylase complexes previously described in a tabular form to demonstrate the normalized spectral abundance factor approach. PMID:16286007 Rco1 and Eaf3 were subunits specific to Rpd3S.