RPD3

Existing Annotations Review

Gene Description

Existing Annotations Review

Core Functions

Zinc-dependent catalytic removal of acetyl groups from histone lysine residues, enabling chromatin compaction and transcriptional regulation

Context-dependent recruitment to repressed loci (HMR, HML, rDNA, intragenic regions) to establish transcriptional silencing

Removal of repressive acetylation at heat-responsive and anaerobic genes to permit activator access

References

Deep Research

Falcon

SGD

SGD gene description for RPD3 (yeast)

📚 Additional Documentation

Notes

Curated Final Recommendations

Curation Files Index

Curation Summary

Review Completion Summary

📄 View Raw YAML

GO Term	Evidence	Action	Reason
GO:0004407 histone deacetylase activity	IBA GO_REF:0000033	ACCEPT	Summary: The PTN008143312 PAINT inference captures Rpd3's conserved, core class I histone deacetylase activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008143312 · conserved class I histone deacetylase node SUPPORTS TRANSFER PTHR10625 places GO:0004407 at a broad ancestral HDAC node seeded by experimentally annotated fungal, metazoan, plant, and slime-mold descendants, including S. cerevisiae RPD3 itself, so the node-level inference matches Rpd3's catalytic core function. Supporting Evidence: PMID:12110674 the ER motif regions of Esa1 or Rpd3 are required for HAT activity of Esa1 or HDAC activity of Rpd3, respectively. PMID:37244892 cryo-EM structure of this prototypical HDAC complex that is characterized by as many as seven subunits performing scaffolding roles for the tight integration of the only catalytic subunit, Rpd3.
GO:0031507 heterochromatin formation	IBA GO_REF:0000033	MODIFY	Summary: The broad heterochromatin-formation IBA transfers positive heterochromatin assembly biology from other HDACs; budding-yeast Rpd3 instead antagonizes Sir-dependent spreading at silent-chromatin boundaries. Reason: The PTN000743059 PAINT node transfers GO:0031507 from fly Rpd3 and human HDAC1/HDAC2. In budding yeast, Rpd3 should not be read as a Sir complex factor that nucleates or spreads silent chromatin; direct experiments show that Rpd3L counteracts Sir2-dependent silencing at HM and telomeric boundaries and that RPD3 deletion enhances, rather than establishes, silencing at HM, telomeric, and rDNA loci. The PAINT node therefore crosses a regulatory-sign boundary: the source HDACs promote heterochromatin formation, whereas the S. cerevisiae evidence supports Rpd3-dependent heterochromatin boundary formation and negative regulation of silent chromatin formation. Propagation Review Root cause: PROPAGATION BAD Failure modes: REGULATORY SIGN INVERSION Sources checked: PANTHER:PTN000743059 · HDAC1/HDAC2/Rpd3 heterochromatin-formation node SUPPORTS SOURCE BUT NOT TARGET The node transfers a broad heterochromatin-formation process from Drosophila Rpd3 and human HDAC1/HDAC2, but the S. cerevisiae evidence points the opposite way; Rpd3 antagonizes Sir-dependent heterochromatin spreading at silent-locus boundaries. Proposed replacements: heterochromatin boundary formation Supporting Evidence: PMID:10388812 deletion of the SIN3 and RPD3 genes enhances silencing, implying that the Sin3-Rpd3 complex functions to counteract, rather than to establish or maintain, silencing. PMID:19372273 Rpd3p-mediated heterochromatin boundary regulation. Together, these data provide insight into the molecular mechanisms for the anti-silencing functions of Rpd3p during the formation of heterochromatin boundaries.
GO:0070210 Rpd3L-Expanded complex	IBA GO_REF:0000033	ACCEPT	Summary: The fungal PTN000835673 PAINT inference correctly transfers Rpd3L-Expanded complex membership to budding-yeast Rpd3. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000835673 · fungal Rpd3L-Expanded complex node SUPPORTS TRANSFER PTHR10625 places GO:0070210 at a fungal node seeded by PomBase clr6, consistent with Rpd3 as a conserved catalytic subunit of Sin3/Rpd3L-type histone deacetylase complexes; S. cerevisiae RPD3 also has same-term direct proteomic evidence for the Rpd3L-Expanded complex.
GO:0004407 histone deacetylase activity	IEA GO_REF:0000120	ACCEPT	Summary: InterPro/RHEA EC mapping to EC:3.5.1.98; valid automatic annotation
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Primary localization annotation from UniProt; non-redundant
GO:0006325 chromatin organization	IEA GO_REF:0000043	ACCEPT	Summary: Valid functional classification; captures Rpd3's role in chromatin state regulation
GO:0006351 DNA-templated transcription	IEA GO_REF:0000043	ACCEPT	Summary: Appropriate parent term; all Rpd3 functions ultimately involve transcription
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine learning inference; valid general classification
GO:0010557 positive regulation of macromolecule biosynthetic process	IEA GO_REF:0000117	ACCEPT	Summary: Rpd3-mediated gene activation increases protein synthesis of target genes
GO:0016787 hydrolase activity	IEA GO_REF:0000043	ACCEPT	Summary: Appropriate parent term for deacetylase activity; not redundant
GO:0032221 Rpd3S complex	IEA GO_REF:0000117	ACCEPT	Summary: ARBA inference; supported by IDA evidence in lines 142-143
GO:0033698 Rpd3L complex	IEA GO_REF:0000117	ACCEPT	Summary: ARBA inference; supported by IDA/HDA evidence in other lines
GO:0003713 transcription coactivator activity	IMP PMID:14737171 The MAPK Hog1 recruits Rpd3 histone deacetylase to activate ...	ACCEPT	Summary: Context-dependent coactivator function - MAPK Hog1 recruits Rpd3 to activate osmoresponsive genes Supporting Evidence: PMID:14737171 The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes.
GO:0003713 transcription coactivator activity	IPI PMID:14737171 The MAPK Hog1 recruits Rpd3 histone deacetylase to activate ...	ACCEPT	Summary: Physical interaction with Hog1 MAPK during gene activation Supporting Evidence: PMID:14737171 The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes.
GO:0003714 transcription corepressor activity	IMP PMID:9150136 Repression by Ume6 involves recruitment of a complex contain...	ACCEPT	Summary: Primary corepressor function - Rpd3 recruited by Ume6 to repress target genes Supporting Evidence: PMID:9150136 Repression by Ume6 involves recruitment of a complex containing Sin3 corepressor and Rpd3 histone deacetylase to target promoters.
GO:0003714 transcription corepressor activity	IPI PMID:9150136 Repression by Ume6 involves recruitment of a complex contain...	ACCEPT	Summary: Physical interaction with Ume6 repressor during recruitment Supporting Evidence: PMID:9150136 Repression by Ume6 involves recruitment of a complex containing Sin3 corepressor and Rpd3 histone deacetylase to target promoters.
GO:0141221 histone deacetylase activity, hydrolytic mechanism	IEA GO_REF:0000120	ACCEPT	Summary: InterPro/RHEA mapping correctly identifies hydrolytic zinc-dependent mechanism
GO:0016479 negative regulation of transcription by RNA polymerase I	IMP PMID:14609951 Chromatin-mediated regulation of nucleolar structure and RNA...	ACCEPT	Summary: Foundational paper establishing Rpd3 repression as core function Supporting Evidence: PMID:14609951 Chromatin-mediated regulation of nucleolar structure and RNA Pol I localization by TOR.
GO:0033698 Rpd3L complex	IDA PMID:16286007 Histone H3 methylation by Set2 directs deacetylation of codi...	ACCEPT	Summary: Direct identification of Rpd3L complex via histone H3K36 methylation-directed recruitment to coding regions Supporting Evidence: PMID:16286007 Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. file:yeast/RPD3/RPD3-deep-research-falcon.md It showed Rpd3 is the sole catalytic subunit and that the complex is organized as an asymmetric dimer in which two copies each of Sin3, Rpd3, and Ume1 form two lobes. Importantly, it found that the active site of one Rpd3 is occluded by a leucine from Rxt2, indicating complex-mediated regulation of catalytic accessibility. file:yeast/RPD3/RPD3-deep-research-falcon.md Rpd3L is described as acting primarily at promoters, performing localized deacetylation near recruitment sites of DNA-binding factors.
GO:0033698 Rpd3L complex	IDA PMID:16286008 Cotranscriptional set2 methylation of histone H3 lysine 36 r...	ACCEPT	Summary: Core finding: Rpd3L essential for heat stress response and survival Supporting Evidence: PMID:16286008 Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex.
GO:0033698 Rpd3L complex	IDA PMID:16314178 Stable incorporation of sequence specific repressors Ash1 an...	ACCEPT	Summary: Direct observation of catalytic activity; biochemical data Supporting Evidence: PMID:16314178 Stable incorporation of sequence specific repressors Ash1 and Ume6 into the Rpd3L complex.
GO:0034503 protein localization to nucleolar rDNA repeats	IMP PMID:17203076 Nutrient starvation promotes condensin loading to maintain r...	ACCEPT	Summary: Mutant phenotype demonstrates functional requirement for deacetylation Supporting Evidence: PMID:17203076 Nutrient starvation promotes condensin loading to maintain rDNA stability.
GO:0045128 negative regulation of reciprocal meiotic recombination	IMP PMID:18515193 The histone methylase Set2p and the histone deacetylase Rpd3...	ACCEPT	Summary: Mutant phenotype data showing Rpd3 deacetylase function is required Supporting Evidence: PMID:18515193 The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:15254041 Redundant mechanisms are used by Ssn6-Tup1 in repressing chr...	ACCEPT	Summary: Mutant phenotype; deacetylase activity required for repression Supporting Evidence: PMID:15254041 Redundant mechanisms are used by Ssn6-Tup1 in repressing chromosomal gene transcription in Saccharomyces cerevisiae.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:17210643 Direct role for the Rpd3 complex in transcriptional inductio...	ACCEPT	Summary: Direct substrate evidence: H4 K5 deacetylation by Rpd3 Supporting Evidence: PMID:17210643 Direct role for the Rpd3 complex in transcriptional induction of the anaerobic DAN/TIR genes in yeast.
GO:0045944 positive regulation of transcription by RNA polymerase II	IGI PMID:17210643 Direct role for the Rpd3 complex in transcriptional inductio...	ACCEPT	Summary: Direct evidence of Rpd3-mediated rDNA condensation under nutrient stress Supporting Evidence: PMID:17210643 Direct role for the Rpd3 complex in transcriptional induction of the anaerobic DAN/TIR genes in yeast.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:17296735 Histone deacetylases RPD3 and HOS2 regulate the transcriptio...	ACCEPT	Summary: Genetic interaction with kinases controlling S-phase; cell cycle-specific function Supporting Evidence: PMID:17296735 Histone deacetylases RPD3 and HOS2 regulate the transcriptional activation of DNA damage-inducible genes.
GO:0045944 positive regulation of transcription by RNA polymerase II	IGI PMID:17296735 Histone deacetylases RPD3 and HOS2 regulate the transcriptio...	ACCEPT	Summary: IGI with different kinase partner (S000006037); different mechanistic context Supporting Evidence: PMID:17296735 Histone deacetylases RPD3 and HOS2 regulate the transcriptional activation of DNA damage-inducible genes.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:17706600 Regulation of the HAP1 gene involves positive actions of his...	ACCEPT	Summary: Physical interaction with transcription factor S000005609 during G1/S Supporting Evidence: PMID:17706600 Regulation of the HAP1 gene involves positive actions of histone deacetylases.
GO:0061186 negative regulation of silent mating-type cassette heterochromatin formation	IMP PMID:10388812 A general requirement for the Sin3-Rpd3 histone deacetylase ...	ACCEPT	Summary: Loss of RPD3 enhances silent mating-type, telomeric, and rDNA silencing. Reason: Sun and Hampsey found that rpd3 mutants show enhanced, rather than reduced, silencing across HM, telomeric, and rDNA reporters, supporting a negative role for Rpd3 in silent-chromatin formation. Supporting Evidence: PMID:10388812 Here we demonstrate that Sin3, Rpd3, and Sap30, a novel component of the Sin3-Rpd3 complex, affect silencing not only at the HMR and telomeric loci, but also at the rDNA locus.
GO:0061186 negative regulation of silent mating-type cassette heterochromatin formation	IMP PMID:10512855 Modulation of life-span by histone deacetylase genes in Sacc...	ACCEPT	Summary: RPD3 deletion enhances silencing at HM, subtelomeric, and rDNA loci. Reason: Kim et al. independently observed enhanced chromatin silencing at the silent mating-type loci, subtelomeric loci, and rDNA in rpd3 deletion cells. Supporting Evidence: PMID:10512855 Deletion of the histone deacetylase gene RPD3 extended life-span. Its effects on chromatin functional state were evidenced by enhanced silencing at the three known heterochromatic regions of the genome, the silent mating type (HM), subtelomeric, and rDNA loci, which occurred even in the absence of SIR3.
GO:0061186 negative regulation of silent mating-type cassette heterochromatin formation	IMP PMID:19372273 Histone deacetylase Rpd3 antagonizes Sir2-dependent silent c...	ACCEPT	Summary: Rpd3 directly deacetylates histone H4 at boundary regions to oppose Sir-dependent spread from silent loci. Reason: Zhou et al. showed that loss of Rpd3 causes defective boundary activity and Sir-dependent repression of HM- and telomere-adjacent regions, directly supporting Rpd3 as a negative regulator of silent mating-type cassette heterochromatin formation. Supporting Evidence: PMID:19372273 We found that disruption of histone deacetylase Rpd3p results in defective boundary activity, leading to a Sir-dependent local propagation of transcriptional repression.
GO:0061188 negative regulation of rDNA heterochromatin formation	IMP PMID:10082585 A genetic screen for ribosomal DNA silencing defects identif...	ACCEPT	Summary: RPD3/HDB mutations increase rDNA silencing by a Sir2-dependent mechanism. Reason: Smith and colleagues identified RPD3-complex mutations as increased rDNA-silencing mutants, supporting Rpd3 as a negative regulator of rDNA heterochromatin formation rather than a positive rDNA silencing factor. Supporting Evidence: PMID:10082585 Mutations in the HDB (RPD3) histone deacetylase complex paradoxically increased rDNA silencing by a SIR2-dependent, SIR3-independent mechanism.
GO:0061188 negative regulation of rDNA heterochromatin formation	IMP PMID:10388812 A general requirement for the Sin3-Rpd3 histone deacetylase ...	ACCEPT	Summary: Loss of RPD3 enhances silent mating-type, telomeric, and rDNA silencing. Reason: Sun and Hampsey found that rpd3 mutants show enhanced rDNA silencing as part of the broader Sin3-Rpd3 anti-silencing phenotype. Supporting Evidence: PMID:10388812 Here we demonstrate that Sin3, Rpd3, and Sap30, a novel component of the Sin3-Rpd3 complex, affect silencing not only at the HMR and telomeric loci, but also at the rDNA locus.
GO:0061188 negative regulation of rDNA heterochromatin formation	IMP PMID:10512855 Modulation of life-span by histone deacetylase genes in Sacc...	ACCEPT	Summary: RPD3 deletion enhances silencing at HM, subtelomeric, and rDNA loci. Reason: Kim et al. independently observed enhanced rDNA silencing after RPD3 deletion, supporting Rpd3 as a negative regulator of rDNA heterochromatin formation. Supporting Evidence: PMID:10512855 Deletion of the histone deacetylase gene RPD3 extended life-span. Its effects on chromatin functional state were evidenced by enhanced silencing at the three known heterochromatic regions of the genome, the silent mating type (HM), subtelomeric, and rDNA loci, which occurred even in the absence of SIR3.
GO:0070822 Sin3-type complex	IDA PMID:9234741 A large protein complex containing the yeast Sin3p and Rpd3p...	ACCEPT	Summary: Rpd3 represses IME2 during meiotic induction; context-specific function Supporting Evidence: PMID:9234741 A large protein complex containing the yeast Sin3p and Rpd3p transcriptional regulators. file:yeast/RPD3/RPD3-deep-research-falcon.md Rpd3 forms two distinct Sin3-associated complexes that target different genomic regions: file:yeast/RPD3/RPD3-deep-research-falcon.md Core: Rpd3 + Sin3 + Ume1 (shared with Rpd3L).
GO:0005737 cytoplasm	IEA GO_REF:0000044	REMOVE	Summary: Inaccurate; RPD3 is nuclear protein; artifact of automatic annotation
GO:0005515 protein binding	IPI PMID:11069890 Ssn6-Tup1 interacts with class I histone deacetylases requir...	REMOVE	Summary: Generic binding term without functional specificity; 61 annotations like this are uninformative Supporting Evidence: PMID:11069890 Ssn6-Tup1 interacts with class I histone deacetylases required for repression.
GO:0005515 protein binding	IPI PMID:11069890 Ssn6-Tup1 interacts with class I histone deacetylases requir...	REMOVE	Summary: Generic binding; see line 16 rationale Supporting Evidence: PMID:11069890 Ssn6-Tup1 interacts with class I histone deacetylases required for repression.
GO:0005515 protein binding	IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy...	REMOVE	Summary: Generic binding; see line 16 rationale Supporting Evidence: PMID:11805837 Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry.