HST1 encodes a nuclear NAD-dependent sirtuin deacetylase recruited by Sum1 and Rfm1 to selected chromosomal loci. Histone deacetylation, prominently at H4K5 and in some contexts H4K16, represses middle-sporulation and metabolic gene programs during vegetative growth and supports efficient initiation at a subset of replication origins. Hst1 also associates with Set3C. Its usual targeting differs from Sir2, but altered targeting in a SUM1-1 background enables Hst1-dependent silencing at the HMR mating-type locus.
Definition: Catalysis of the removal of an acetyl group from lysine 5 of histone H4 using NAD+ as a reactant, producing deacetylated histone, nicotinamide, and 2'-O-acetyl-ADP-ribose.
Justification: Current GO has an H4K5-specific term for the hydrolytic mechanism and several residue-specific NAD-dependent histone deacetylase terms, but no NAD-dependent H4K5 child of GO:0017136. Hst1-specific experiments identify H4K5 as its main histone H4 target.
Parent term: histone deacetylase activity, NAD-dependent
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Hst1 is a nuclear chromatin-associated sirtuin recruited to specific promoters and replication origins. Reason: Nuclear localization and locus-specific chromatin association are supported by PMID:11711434 and PMID:29066473. |
| GO:0006974 DNA damage response | IBA GO_REF:0000033 | UNDECIDED | Summary: A specific Hst1 contribution to DNA-damage response remains unresolved. Reason: The existing general report cites broad sirtuin genome-stability literature, while the Set3C paper establishes complex membership and histone deacetylation without resolving an Hst1-specific DNA-damage mechanism. Locus-specific transcriptional repression does not exclude DNA-damage response, and absence of a retrieved positive experiment does not refute the ancestral inference or NAS annotation. A focused role-specific assessment is pending. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000872222 · PTN000872222 UNRESOLVED The Sir2/sirtuin DNA-damage IBD is recovered; target-specific divergence in recruitment does not itself establish loss of every damage-response contribution. |
| GO:0003714 transcription corepressor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Hst1 provides catalytic repression within the Sum1-Rfm1-Hst1 complex. Reason: Rfm1 recruits Hst1 to Sum1-bound promoters to repress middle-sporulation genes (PMID:12612074). Supporting Evidence: PMID:12612074 Rfm1 interacts with both Sum1 and Hst1 and is required for the Sum1-Hst1 interaction. |
| GO:0031509 subtelomeric heterochromatin formation | IBA GO_REF:0000033 | UNDECIDED | Summary: Native Hst1 subtelomeric participation and telomeric association remain unresolved. Reason: Hst1 and Sir2 differ in their normal recruitment partners, and PMID:8810037 reports no HST1-deletion phenotype in the tested HML/rDNA assays. Those results do not directly exclude every subtelomeric context or telomeric association. PMID:17242192 shows targeting-specific rather than necessarily catalytic divergence, and SUM1-1 reveals conditional Hst1 silencing capacity. The inherited subtelomeric assertion and its derived location need assessment at the actual telomeric context rather than categorical rejection from the principal gene-specific role. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000872222 · PTN000872222 UNRESOLVED Subtelomeric IBD recovered. Distinct usual cofactors are relevant but do not establish absence in all native or conditional subtelomeric contexts. Supporting Evidence: PMID:17242192 the differences in the silencing and repression functions of Sir2 and Hst1 may not be due to differences in enzymatic activities of the proteins |
| GO:0032041 histone H3K14 deacetylase activity, NAD-dependent | IBA GO_REF:0000033 | UNDECIDED | Summary: Hst1 H3-site deacetylation is not excluded by preferential H4K5 targeting. Reason: The prior rationale cited an H4-focused locus study as evidence against H3K9/H3K14, which is not a valid substrate-exclusion argument. The IBA supplies conserved sirtuin capacity, PMID:11711434 reports broad histone substrates for Hst1-containing complexes, and PMID:17242192 emphasizes cofactor-targeting differences rather than catalytic differences from Sir2. Nevertheless, the reviewed sources do not resolve each H3 lysine for purified Hst1 or a defined Hst1-dependent locus; retain uncertainty pending site-specific adjudication. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000872222 · PTN000872222 UNRESOLVED Site-specific sirtuin IBD recovered. H4K5 predominance does not demonstrate loss of H3-site catalysis; target-specific site evidence remains unresolved. Supporting Evidence: PMID:11711434 the activities associated with Set3C and Hst1–Sum1 complex deacetylate several histone substrates in vitro with no apparent substrate specificity PMID:17242192 the differences in the silencing and repression functions of Sir2 and Hst1 may not be due to differences in enzymatic activities of the proteins |
| GO:0046969 histone H3K9 deacetylase activity, NAD-dependent | IBA GO_REF:0000033 | UNDECIDED | Summary: Hst1 H3-site deacetylation is not excluded by preferential H4K5 targeting. Reason: The prior rationale cited an H4-focused locus study as evidence against H3K9/H3K14, which is not a valid substrate-exclusion argument. The IBA supplies conserved sirtuin capacity, PMID:11711434 reports broad histone substrates for Hst1-containing complexes, and PMID:17242192 emphasizes cofactor-targeting differences rather than catalytic differences from Sir2. Nevertheless, the reviewed sources do not resolve each H3 lysine for purified Hst1 or a defined Hst1-dependent locus; retain uncertainty pending site-specific adjudication. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000872222 · PTN000872222 UNRESOLVED Site-specific sirtuin IBD recovered. H4K5 predominance does not demonstrate loss of H3-site catalysis; target-specific site evidence remains unresolved. Supporting Evidence: PMID:11711434 the activities associated with Set3C and Hst1–Sum1 complex deacetylate several histone substrates in vitro with no apparent substrate specificity PMID:17242192 the differences in the silencing and repression functions of Sir2 and Hst1 may not be due to differences in enzymatic activities of the proteins |
| GO:0046970 histone H4K16 deacetylase activity, NAD-dependent | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Hst1-dependent H4K16 deacetylation is supported at a subset of tested origins. Reason: PMID:18990212 says H4K16 is not a general target, but immediately reports significantly higher H4K16 acetylation at ARS1223 and ARS1511 in both hst1Δ and sum1Δ strains. This context-specific target evidence complements the inherited catalytic inference. H4K5 remains the predominant substrate in the broader tested set; predominance is not exclusivity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000872222 · PTN000872222 SUPPORTS TRANSFER The H4K16 IBD is supported by target-specific locus acetylation changes, retained as context-dependent alongside preferred H4K5 activity. Supporting Evidence: PMID:18990212 Only ARS1223 and ARS1511 showed a significant higher H4 K16 acetylation level in both sum1Δ and hst1Δ yeast strains |
| GO:0000781 chromosome, telomeric region | IEA GO_REF:0000108 | UNDECIDED | Summary: Native Hst1 subtelomeric participation and telomeric association remain unresolved. Reason: Hst1 and Sir2 differ in their normal recruitment partners, and PMID:8810037 reports no HST1-deletion phenotype in the tested HML/rDNA assays. Those results do not directly exclude every subtelomeric context or telomeric association. PMID:17242192 shows targeting-specific rather than necessarily catalytic divergence, and SUM1-1 reveals conditional Hst1 silencing capacity. The inherited subtelomeric assertion and its derived location need assessment at the actual telomeric context rather than categorical rejection from the principal gene-specific role. Supporting Evidence: PMID:17242192 the differences in the silencing and repression functions of Sir2 and Hst1 may not be due to differences in enzymatic activities of the proteins |
| GO:0000785 chromatin | IEA GO_REF:0000117 | ACCEPT | Summary: Hst1 is recruited to chromatin at Sum1-regulated promoters and selected replication origins. Reason: Chromatin association and locus-specific loss of Hst1 binding are directly demonstrated in PMID:29066473. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Hst1 localizes to the nucleus, where it acts on promoter chromatin. Reason: Nuclear localization is experimentally supported and coherent with its chromatin-targeted repression. |
| GO:0017136 histone deacetylase activity, NAD-dependent | IEA GO_REF:0000117 | ACCEPT | Summary: NAD-dependent histone deacetylation is Hst1's core catalytic activity. Reason: Direct genetic and biochemical studies establish Hst1-dependent histone deacetylation (PMID:11313477; PMID:12972620). Supporting Evidence: PMID:12972620 The NAD(+)-dependent deacetylase activity of Hst1p represses de novo NAD(+) biosynthesis genes in the absence of new protein synthesis, suggesting a direct effect. |
| GO:0030466 silent mating-type cassette heterochromatin formation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Hst1 supports mating-type silencing under altered SUM1-1 targeting. Reason: The electronic term is compatible with the experimentally established non-core SUM1-1/HMR context. Lack of the condition in this broad annotation does not make the process false; the conditional context is stated here, as for the IMP/IGI rows. Supporting Evidence: PMID:11313477 Sum1-1 requires the Sir2 homolog, Hst1, for silencing |
| GO:0031981 nuclear lumen | IEA GO_REF:0000117 | ACCEPT | Summary: The nuclear-lumen assignment is compatible with Hst1's core chromatin-associated activity. Reason: Nuclear localization and chromatin binding support this broad compartment. A more specific chromatin annotation does not make nuclear lumen non-core. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Hst1 catalyzes NAD-dependent lysine deacetylation of protein substrates, physiologically including promoter histones. Reason: This activity-level term accurately captures the sirtuin reaction without overcommitting to an unsupported histone residue. Supporting Evidence: PMID:12972620 The NAD(+)-dependent deacetylase activity of Hst1p represses de novo NAD(+) biosynthesis genes in the absence of new protein synthesis, suggesting a direct effect. |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000108 | ACCEPT | Summary: Hst1 represses specific RNA polymerase II transcription programs through promoter histone deacetylation. Reason: Middle-sporulation, NAD-biosynthesis and thiamine-biosynthesis genes are directly repressed through Hst1-dependent chromatin deacetylation. These are target programs of the established transcriptional corepressor mechanism. Supporting Evidence: PMID:10562556 SUM1 and HST1, genes previously associated with transcriptional silencing, are required for MSE-mediated repression. |
| GO:0045910 negative regulation of DNA recombination | IEA GO_REF:0000117 | UNDECIDED | Summary: Recombination suppression requires locus- and condition-specific adjudication. Reason: The absence of an rDNA phenotype in one HST1-disruption study cannot exclude all DNA recombination contexts. The experimental mitotic-recombination annotation (PMID:16051752) remains unresolved because its target-specific full-text evidence is unavailable; the broader electronic claim should share that uncertainty rather than be rejected as contradicted. Supporting Evidence: PMID:8810037 Disruption of HST1 has shown no phenotype with respect to mechanisms in which SIR2 has a role |
| GO:0070403 NAD+ binding | IEA GO_REF:0000002 | ACCEPT | Summary: NAD+ binding is intrinsic to the Hst1 sirtuin catalytic cycle. Reason: Hst1 consumes NAD+ during deacetylation, and PMID:12972620 directly reports its comparatively low NAD+ affinity. Supporting Evidence: PMID:12972620 In vitro experiments demonstrate that Hst1p has relatively low affinity toward NAD(+) in comparison to other NAD(+)-dependent enzymes. |
| GO:0005515 protein binding | IPI PMID:12612074 Rfm1, a novel tethering factor required to recruit the Hst1 ... | REMOVE | Summary: Generic protein binding does not specify Hst1's mechanistic activity. Reason: The interaction is retained as evidence; generic protein binding is removed for lack of functional information, not because complex association is false. Hst1's NAD-dependent deacetylase and corepressor activities are supported separately. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: Generic protein binding does not specify Hst1's mechanistic activity. Reason: The interaction is retained as evidence; generic protein binding is removed for lack of functional information, not because complex association is false. Hst1's NAD-dependent deacetylase and corepressor activities are supported separately. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Generic protein binding does not specify Hst1's mechanistic activity. Reason: The interaction is retained as evidence; generic protein binding is removed for lack of functional information, not because complex association is false. Hst1's NAD-dependent deacetylase and corepressor activities are supported separately. |
| GO:0005634 nucleus | IDA PMID:11711434 The S. cerevisiae SET3 complex includes two histone deacetyl... | ACCEPT | Summary: Hst1 is experimentally localized to the nucleus. Reason: Nuclear localization is supported by the established chromatin-associated repression mechanism. The retrieved Set3C full text establishes Hst1-containing chromatin-regulatory complexes rather than an explicit localization-imaging experiment; this does not undermine the location itself. Supporting Evidence: PMID:11711434 We also conclude that Hst1 is present in two distinct complexes, Set3C and the Hst1–Sum1 complex. file:yeast/HST1/HST1-deep-research-openscientist.md Functionally, Hst1 acts in the **nucleus, on chromatin**. |
| GO:0006974 DNA damage response | NAS PMID:11711434 The S. cerevisiae SET3 complex includes two histone deacetyl... | UNDECIDED | Summary: A specific Hst1 contribution to DNA-damage response remains unresolved. Reason: The existing general report cites broad sirtuin genome-stability literature, while the Set3C paper establishes complex membership and histone deacetylation without resolving an Hst1-specific DNA-damage mechanism. Locus-specific transcriptional repression does not exclude DNA-damage response, and absence of a retrieved positive experiment does not refute the ancestral inference or NAS annotation. A focused role-specific assessment is pending. |
| GO:0009267 cellular response to starvation | NAS PMID:11711434 The S. cerevisiae SET3 complex includes two histone deacetyl... | KEEP AS NON CORE | Summary: Nutrient state modulates Hst1-regulated sporulation and metabolic transcription programs. Reason: Starvation response is biologically relevant to relief of sporulation repression but is downstream of Hst1's catalytic core function. |
| GO:0034967 Set3 complex | IPI PMID:11711434 The S. cerevisiae SET3 complex includes two histone deacetyl... | KEEP AS NON CORE | Summary: Hst1 is an experimentally identified Set3C subunit, although it is largely dispensable for Set3C repression. Reason: PMID:11711434 places Hst1 in Set3C but identifies the Sum1-Rfm1-Hst1 complex as the stronger Hst1-dependent context. Supporting Evidence: PMID:11711434 The S. cerevisiae SET3 complex includes two histone deacetylases, Hos2 and Hst1, and is a meiotic-specific repressor of the sporulation gene program. |
| GO:0045835 negative regulation of meiotic nuclear division | IDA PMID:11711434 The S. cerevisiae SET3 complex includes two histone deacetyl... | UNDECIDED | Summary: The specific Hst1 contribution to repression of meiotic division requires clarification. Reason: PMID:11711434 finds Hst1 dispensable for the tested Set3C-mediated early-meiotic repression. That challenges an essential Set3C interpretation, but does not show that a nonessential catalytic subunit cannot contribute or negate Sum1/Hst1 repression in a different stage/context. The source IDA is retained as unresolved pending the precise assay-to-term interpretation. Supporting Evidence: PMID:11711434 Deletion of hst1 did not relieve repression of ime2 or ndt80 |
| GO:0000118 histone deacetylase complex | IPI PMID:11711434 The S. cerevisiae SET3 complex includes two histone deacetyl... | ACCEPT | Summary: Hst1 is the catalytic subunit of promoter-targeted histone deacetylase complexes. Reason: Physical association with Sum1-Rfm1 and Set3C supports membership in histone deacetylase complexes. Supporting Evidence: PMID:11711434 TAP purification of the substoicheiometric component Hst1 yielded all seven proteins of Set3C |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:12612074 Rfm1, a novel tethering factor required to recruit the Hst1 ... | ACCEPT | Summary: Hst1 regulates selected RNA polymerase II genes through local chromatin deacetylation. Reason: PMID:12612074 directly links Sum1-Rfm1 recruitment of Hst1 to repression of middle-sporulation genes. Supporting Evidence: PMID:10562556 SUM1 and HST1, genes previously associated with transcriptional silencing, are required for MSE-mediated repression. |
| GO:0030174 regulation of DNA-templated DNA replication initiation | NAS PMID:18990212 Control of replication initiation by the Sum1/Rfm1/Hst1 hist... | KEEP AS NON CORE | Summary: Hst1 promotes efficient initiation at a subset of Sum1-bound replication origins through histone deacetylation. Reason: PMID:18990212 provides direct Hst1-specific evidence, but origin control is secondary to promoter repression. Supporting Evidence: PMID:18990212 We identified seven ARS elements whose initiation capacity depended on Sum1 and Hst1. |
| GO:0043937 regulation of sporulation | NAS PMID:12612074 Rfm1, a novel tethering factor required to recruit the Hst1 ... | ACCEPT | Summary: Hst1 represses middle-sporulation genes during vegetative growth and thereby regulates the sporulation program. Reason: Sum1-Rfm1 recruits Hst1 to these promoters, and loss of the complex derepresses the program (PMID:12612074). Supporting Evidence: PMID:10562556 SUM1 and HST1, genes previously associated with transcriptional silencing, are required for MSE-mediated repression. |
| GO:0008270 zinc ion binding | RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr... | ACCEPT | Summary: Hst1 contains the conserved structural zinc-binding subdomain of sirtuins. Reason: Zinc binding is a conserved structural feature of the sirtuin catalytic domain and is consistent with the Hst1 sequence/domain annotation. |
| GO:0017136 histone deacetylase activity, NAD-dependent | IDA PMID:11313477 A novel form of transcriptional silencing by Sum1-1 requires... | ACCEPT | Summary: Hst1-dependent NAD-dependent histone deacetylase activity is required for engineered Sum1-1 silencing. Reason: PMID:11313477 directly tested the requirement for Hst1 in this conditional silencing system. |
| GO:0017136 histone deacetylase activity, NAD-dependent | IDA PMID:11711434 The S. cerevisiae SET3 complex includes two histone deacetyl... | ACCEPT | Summary: Hst1 is one of the histone deacetylases identified in Set3C. Reason: PMID:11711434 experimentally identifies Hst1 in the complex and supports NAD-dependent histone deacetylase activity. Supporting Evidence: PMID:11711434 These results indicate that Hos2 in Set3C and Hst1 in both Set3C and the Hst1–Sum1 complexes are active histone deacetylases. |
| GO:0030466 silent mating-type cassette heterochromatin formation | IGI PMID:27185881 Determinants of Sir2-Mediated, Silent Chromatin Cohesion. | KEEP AS NON CORE | Summary: The cited paper directly examines full-length Hst1 at HMR under SUM1-1 targeting. Reason: PubMed figure captions for PMID:27185881 describe full-length Hst1-dependent HMR cohesion and cohesin recruitment in sir2Δ/SUM1-1 cells, including hst1Δ controls. Together with PMID:11313477, this supports the curator's conditional HMR-silencing framing. Its Sir2-centered abstract was incomplete evidence for the Hst1 experiments, and the engineered targeting context remains non-core. Supporting Evidence: file:yeast/HST1/HST1-PMID27185881-pubmed-figures.md Full-length HST1 mediates cohesion at HMR in a SUM1-1 background. PMID:11313477 Sum1-1 requires the Sir2 homolog, Hst1, for silencing |
| GO:0030466 silent mating-type cassette heterochromatin formation | IMP PMID:11313477 A novel form of transcriptional silencing by Sum1-1 requires... | KEEP AS NON CORE | Summary: Hst1 is required for HMR silencing when recruited by the gain-of-function Sum1-1 protein. Reason: PMID:11313477 supports the annotation in this engineered context, but native Hst1 does not normally perform regional mating-type silencing. |
| GO:0030466 silent mating-type cassette heterochromatin formation | IGI PMID:11313477 A novel form of transcriptional silencing by Sum1-1 requires... | KEEP AS NON CORE | Summary: Genetic evidence supports Hst1-dependent Sum1-1 silencing at HMR. Reason: Retain the experimentally curated interaction while making the non-native targeting context explicit. |
| GO:0034967 Set3 complex | IDA PMID:11711434 The S. cerevisiae SET3 complex includes two histone deacetyl... | KEEP AS NON CORE | Summary: Hst1 is an experimentally identified Set3C component. Reason: Set3C membership is real, but Hst1 is not essential for the complex's meiotic repression and its main complex is Sum1-Rfm1-Hst1. |
| GO:0045950 negative regulation of mitotic recombination | IMP PMID:16051752 HST2 mediates SIR2-independent life-span extension by calori... | UNDECIDED | Summary: The cached abstract focuses on Hst2-mediated lifespan regulation and does not expose the experiment supporting Hst1-dependent recombination control. Reason: The IMP annotation should not be overruled without the relevant full-text evidence; retain for curator follow-up. |
| GO:0070623 regulation of thiamine biosynthetic process | IMP PMID:20439498 Thiamine biosynthesis in Saccharomyces cerevisiae is regulat... | ACCEPT | Summary: Hst1 directly regulates a metabolic transcriptional program for thiamine biosynthesis. Reason: PMID:20439498 ties THI-gene regulation to the NAD-dependent Hst1 repression mechanism. A different target-gene set is part of this core promoter-regulatory activity, rather than intrinsically non-core because sporulation genes are also targets. Supporting Evidence: PMID:20439498 We have determined that multiple thiamine ( THI ) genes in Saccharomyces cerevisiae are also regulated by the intracellular NAD + concentration via the NAD + -dependent histone deacetylase (HDAC) Hst1 and, to a lesser extent, Sir2. |
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Download this section (compressed HTML)Q: Do native Hst1 complexes participate directly in DNA-damage response or DNA recombination control, and if so through chromatin or non-histone substrates?
Q: How does the Sum1-Rfm1-Hst1 complex choose between middle-sporulation, NAD-biosynthesis, thiamine-biosynthesis, and replication-origin targets as nutrient state and intracellular NAD+ change?
Experiment: Combine acute Hst1 depletion with calibrated residue-specific histone acetylation profiling and Hst1/Sum1 ChIP-seq across vegetative, NAD-limited, and sporulation-inducing conditions, then test catalytic-dead Hst1 rescue at directly bound loci.
Hypothesis: Hst1 substrate use depends on locus, cofactors and physiological state; H4K5 predominates at many tested sites, H4K16 is supported at a subset, and H3K9/H3K14 activity requires a site-specific test.
Type: acute depletion, quantitative histone acetyl-proteomics, and ChIP-seq
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Download this section (compressed HTML)Source: Determinants of Sir2-Mediated, Silent Chromatin Cohesion, accessed 2026-09-20 through the web tool. The standard publication fetch returned an abstract-only cache; PubMed separately exposes figure captions.
Figure 1 caption excerpt:
Full-length HST1 mediates cohesion at HMR in a SUM1-1 background.
The caption describes wild-type, sir2 deletion, sir2 deletion/SUM1-1, and sir2 deletion/SUM1-1/hst1 deletion strains. It also identifies a cohesin ChIP comparison at HMR in this background. Thus the Hst1 evidence is in the paper despite its Sir2-centered title and abstract. This supports the existing conditional, non-core HMR-silencing annotation in conjunction with PMID:11313477; it does not establish native telomeric recruitment of Hst1.
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