quiescent telomere hypercluster

cellstructuremech:quiescent_telomere_hypercluster · Other · Nucleoprotein complex · Proposed

A nuclear assembly in which multiple chromosome ends and associated subtelomeric chromatin coalesce into fewer enlarged foci during quiescence, characterized in Saccharomyces cerevisiae and Schizosaccharomyces pombe. Nuclear position and assembly requirements depend on species, strain and starvation conditions. [DOI:10.1186/s13059-015-0766-2]

Multipanel figure: Rap1-GFP foci across growth states, colocalization with subtelomeric Y-prime FISH, a sir3-deletion comparison, and central Rap1-marked hyperclusters relative to the Nup49-marked envelope. Growth and nuclear-zoning diagrams and quantification accompany the micrographs. OTHER · *Saccharomyces cerevisiae* (`NCBITaxon:4932`) · Micol Guidi, Myriam Ruault, Martial Marbouty, Isabelle Loïodice, Axel Cournac, Cyrille Billaudeau, Antoine Hocher, Julien Mozziconacci, Romain Koszul, Angela Taddei; CC BY 4.0, via PubMed Central; unmodified Figure 1. · CC_BY_4_0 · source: PMC PMC4581094.1 Fig1 · `DOI:10.1186/s13059-015-0766-2`

Synonyms: telomere hypercluster; telomeric hypercluster

Part of: nucleus (GO:0005634)

Has part: GO:0000781 — chromosome, telomeric region (no local record); GO:0099115 — chromosome, subtelomeric region (no local record)

UniProt location names: UniProt Consortium, CC BY 4.0. Reference label and route sources.

Components

Component	Type	Part of / acts on	Grounding	Genes	Essential	Role
telomere	Dna	part of	`SO:0000624`		UNKNOWN	Chromosome-end DNA brought together within the nuclear assembly. `DOI:10.1093/nar/gkaa043` Taz1-marked chromosome ends form fewer, brighter foci on nitrogen starvation; this is not a claim that every chromosome end is individually resolved.
subtelomere	Dna	part of	`SO:0001997`		UNKNOWN	Subtelomeric DNA associated with the coalescing chromosome ends. `DOI:10.1186/s13059-015-0766-2` Y-prime FISH and chromosome-contact mapping establish subtelomeric association; a Y-prime probe does not label every chromosome end equally.
nucleosome	Other	part of	`GO:0000786`		UNKNOWN	DNA-histone packing unit of the associated subtelomeric chromatin. `DOI:10.1091/mbc.E16-01-0069` Histone H4 tail and K16 substitutions implicate nucleosomal chromatin in hypercluster formation. This is a chromatin-class assertion, not an isoform-specific localization or copy-number measurement.
Sirtuin family	Protein	part of	`InterPro:IPR003000`	SIR2	UNKNOWN	Sir2-class chromatin factor detected in budding-yeast telomere hyperclusters. `DOI:10.1091/mbc.E16-01-0069` Sir2-GFP overlaps telomeric FISH and Sir3/Rap1 foci; sir2 deletion impairs formation in the tested background. Separate nucleolar Sir2 signal must not be called a telomere cluster.
Sir3-like silencing protein	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	SIR3	UNKNOWN	Budding-yeast chromatin constituent supporting telomere coalescence. `DOI:10.1186/s13059-015-0766-2` Sir3-GFP clusters with telomeres; sir3 deletion removes hyperclustering and increased intertelomeric contacts. Requirement does not prove increased Sir3 abundance or a unique molecular crosslinking reaction.
Sir4-like silencing protein	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	SIR4	UNKNOWN	Budding-yeast SIR constituent associated with clustered chromosome ends. `DOI:10.1186/s13059-015-0766-2` Sir4-GFP shows hyperclusters; SIR4 deletion disrupts their formation in stationary-phase budding yeast.
TE2IP/Rap1	Protein	part of	`InterPro:IPR039595`	RAP1	UNKNOWN	Telomere-associated Rap1 class; the curated direct-localization example is from budding yeast. `DOI:10.1186/s13059-015-0766-2` Rap1-GFP foci coalesce and overlap Y-prime FISH and Sir3. Rap1 abundance does not increase with the brighter clusters.
Ku80	Protein	part of	`InterPro:IPR024193`	YKU80	DISPENSABLE	Ku80-class protein detected at budding-yeast hyperclusters without a single-deletion assembly requirement. `DOI:10.1091/mbc.E16-01-0069` Yku80 colocalizes with hyperclusters; its deletion does not prevent formation or peripheral positioning in the tested conditions.
Taz1-like telomere-binding protein	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	taz1	UNKNOWN	Fission-yeast chromosome-end constituent used to image hyperclustering. `DOI:10.1093/nar/gkaa043` Taz1-GFP marks the bright focus in nitrogen-starved cells; its signal weakens as telomeres erode.
Heterochromatin-associated chromo domain-containing protein	Protein	part of	`InterPro:IPR051219`	swi6	UNKNOWN	Swi6-class constituent of fission-yeast subtelomeric heterochromatin followed during hyperclustering. `DOI:10.1093/nar/gkaa043` Figure 2 follows Swi6-GFP telomere/subtelomere clusters in wild type and telomerase-deficient cells. The centromeric Swi6 focus is distinguished with the spindle-pole-body marker.
Esc1-like nuclear-envelope anchoring protein	Protein	acts on	Reviewed label only (reviewed name; no accession asserted)	ESC1	DISPENSABLE	Condition-dependent peripheral positioning machinery for budding-yeast chromosome-end assemblies, not a stoichiometric focus-core constituent. `DOI:10.1091/mbc.E16-01-0069` esc1 deletion leaves hyperclusters present but changes their nuclear position. Peripheral localization and positioning genetics support associated anchoring machinery, not direct residence in the focus core.
Bouquet formation protein 4	Protein	acts on	`InterPro:IPR037548`	bqt4	DISPENSABLE	Fission-yeast nuclear-envelope machinery retaining chromosome ends at the periphery during quiescence. `DOI:10.1093/nar/gkaa043` bqt4 deletion alters G0 telomere position without changing the number of clusters. The established Rap1-Bqt4 tether is distinct from cluster coalescence.

Organism-specific protein examples

Named proteins in which each component's role was established, with the organism the evidence comes from. The component above is the taxon-agnostic family; these are the specific entries behind it.

Sirtuin family

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P06700`	NAD-dependent histone deacetylase SIR2	SIR2	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reference-sequence exemplar; the accession does not imply that the reference stock was the exact experimental strain. `DOI:10.1091/mbc.E16-01-0069` Figure 1 immuno-FISH and dual-color localization identify telomere-associated Sir2. `https://www.uniprot.org/uniprotkb/P06700/entry` Reviewed entry, gene, native label and source taxon verified on 2026-10-05. Structural role is supported by the primary experiment, not inferred from the sequence lookup.

Sir3-like silencing protein

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P06701`	Regulatory protein SIR3	SIR3	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reference-sequence exemplar; the accession does not imply that the reference stock was the exact experimental strain. `DOI:10.1091/mbc.E16-01-0069` Figure 1 directly colocalizes Sir3-RFP with Sir2-marked telomeric foci. `https://www.uniprot.org/uniprotkb/P06701/entry` Reviewed entry, gene, native label and source taxon verified on 2026-10-05. Structural role is supported by the primary experiment, not inferred from the sequence lookup.

Sir4-like silencing protein

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P11978`	Regulatory protein SIR4	SIR4	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reference-sequence exemplar; the accession does not imply that the reference stock was the exact experimental strain. `DOI:10.1186/s13059-015-0766-2` Results report Sir4-GFP localization with the other SIR factors; SIR4 deletion impairs hyperclustering. `https://www.uniprot.org/uniprotkb/P11978/entry` Reviewed entry, gene, native label and source taxon verified on 2026-10-05. Structural role is supported by the primary experiment, not inferred from the sequence lookup.

TE2IP/Rap1

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P11938`	DNA-binding protein RAP1	RAP1	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reference-sequence exemplar; the accession does not imply that the reference stock was the exact experimental strain. `DOI:10.1186/s13059-015-0766-2` Figure 1 tracks Rap1 foci and verifies telomeric/subtelomeric association by FISH. `https://www.uniprot.org/uniprotkb/P11938/entry` Reviewed entry, gene, native label and source taxon verified on 2026-10-05. Structural role is supported by the primary experiment, not inferred from the sequence lookup.

Ku80

Accession	Protein	Gene	Organism	Entry
`UniProtKB:Q04437`	ATP-dependent DNA helicase II subunit 2	YKU80	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reference-sequence exemplar; the accession does not imply that the reference stock was the exact experimental strain. `DOI:10.1091/mbc.E16-01-0069` The nuclear-positioning Results directly report Yku80 hypercluster colocalization; this does not automatically establish Yku70 residence. `https://www.uniprot.org/uniprotkb/Q04437/entry` Reviewed entry, gene, native label and source taxon verified on 2026-10-05. Structural role is supported by the primary experiment, not inferred from the sequence lookup.

Taz1-like telomere-binding protein

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P79005`	Telomere length regulator taz1	taz1	Schizosaccharomyces pombe 972h- (`NCBITaxon:284812`)	REVIEWED
Role and evidence (2 references) Reference-sequence exemplar; the accession does not imply that the reference stock was the exact experimental strain. `DOI:10.1093/nar/gkaa043` Figure 1 compares Taz1-GFP foci in vegetative and nitrogen-starved cells. `https://www.uniprot.org/uniprotkb/P79005/entry` Reviewed entry, gene, native label and source taxon verified on 2026-10-05. Structural role is supported by the primary experiment, not inferred from the sequence lookup.

Heterochromatin-associated chromo domain-containing protein

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P40381`	Chromatin-associated protein swi6	swi6	Schizosaccharomyces pombe 972h- (`NCBITaxon:284812`)	REVIEWED
Role and evidence (2 references) Reference-sequence exemplar; the accession does not imply that the reference stock was the exact experimental strain. `DOI:10.1093/nar/gkaa043` Figure 2 uses Swi6-GFP to retain visibility of subtelomeric chromatin when terminal-repeat Taz1 signal declines. `https://www.uniprot.org/uniprotkb/P40381/entry` Reviewed entry, gene, native label and source taxon verified on 2026-10-05. Structural role is supported by the primary experiment, not inferred from the sequence lookup.

Esc1-like nuclear-envelope anchoring protein

Accession	Protein	Gene	Organism	Entry
`UniProtKB:Q03661`	Silent chromatin protein ESC1	ESC1	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reference-sequence exemplar; the accession does not imply that the reference stock was the exact experimental strain. `DOI:10.1091/mbc.E16-01-0069` Esc1 nuclear-envelope localization and deletion effects support a positioning role; no claim of uniform core occupancy is made. `https://www.uniprot.org/uniprotkb/Q03661/entry` Reviewed entry, gene, native label and source taxon verified on 2026-10-05. Structural role is supported by the primary experiment, not inferred from the sequence lookup.

Bouquet formation protein 4

Accession	Protein	Gene	Organism	Entry
`UniProtKB:O60158`	Bouquet formation protein 4	bqt4	Schizosaccharomyces pombe 972h- (`NCBITaxon:284812`)	REVIEWED
Role and evidence (2 references) Reference-sequence exemplar; the accession does not imply that the reference stock was the exact experimental strain. `DOI:10.1093/nar/gkaa043` Figure 3 and Results provide G0 positioning genetics; the schematic tether is not direct imaging of Bqt4 inside the telomere focus. `https://www.uniprot.org/uniprotkb/O60158/entry` Reviewed entry, gene, native label and source taxon verified on 2026-10-05. Structural role is supported by the primary experiment, not inferred from the sequence lookup.

Canonical examples

NCBITaxon:4932 Saccharomyces cerevisiae — Budding yeast studied in W303 and BY backgrounds. Central hyperclusters in density-enriched quiescent populations and peripheral clusters under other published conditions are retained as distinct observations, not forced into one nuclear position. [DOI:10.1186/s13059-015-0766-2]
NCBITaxon:4896 Schizosaccharomyces pombe — Nitrogen-starved fission yeast forms a predominantly single bright telomeric focus near the nuclear envelope; clustering and envelope attachment are experimentally separable. [DOI:10.1093/nar/gkaa043]

Functions

telomere organization GO:0032200 — Spatial grouping of chromosome ends and associated chromatin during quiescence.
- DOI:10.1186/s13059-015-0766-2 Microscopy and chromosome-contact maps support chromosome-end reorganization.
- DOI:10.1093/nar/gkaa043 Fission-yeast microscopy supports a quiescent redistribution of telomere foci; envelope-dependent TERRA regulation is not assigned to clustering alone.

Mechanism graphs

Condition-dependent budding-yeast hypercluster assembly (ASSEMBLY)

Subject	Predicate	Object	Evidence
Starvation after respiratory growth	stimulates	Telomere hypercluster formation	`DOI:10.1186/s13059-015-0766-2` Carbon-exhaustion, abrupt-starvation and respiration perturbations distinguish metabolic history from slow growth alone. `DOI:10.1101/gr.279874.124` Density-enriched post-diauxic cells transferred to water also form hyperclusters.
Sir3-like silencing protein	supports	Telomere hypercluster formation	`DOI:10.1186/s13059-015-0766-2` Deletion and chromosome-contact experiments support the assembly requirement, without proving increased protein abundance.
Assembly-compatible histone H4 K16 state	supports	Telomere hypercluster formation	`DOI:10.1091/mbc.E16-01-0069` Histone substitutions support a chromatin-state contribution, not direct observation of an exact Sir3 bridging reaction.

Anchoring is separable from cluster formation (REGULATION)

Subject	Predicate	Object	Evidence
Esc1-like anchoring machinery	supports	Peripheral cluster position in tested budding yeast	`DOI:10.1091/mbc.E16-01-0069` Esc1 deletion separates positioning from cluster formation.
Bouquet formation protein 4	supports	Peripheral cluster position in nitrogen-starved fission yeast	`DOI:10.1093/nar/gkaa043` Figure 3 and Results distinguish envelope position from the number of clusters.

Budding-yeast declustering during quiescence exit (DISASSEMBLY)

Subject	Predicate	Object	Evidence
Nutrient refeeding	stimulates	Telomere hypercluster dispersal	`DOI:10.1091/mbc.E16-01-0069` Cycloheximide, latrunculin A and nocodazole do not prevent dispersal in the reported assay. `DOI:10.1101/gr.279874.124` rpb1-1 inactivation and phenanthroline largely preserve declustering despite impaired transcription. Thiolutin differs and has broader effects.

Discussions

CURATION_TODO (RESOLVED): Keep the multi-chromosome assembly separate from individual telomeres and other nuclear structures.
CURATION_TODO (OPEN): Find exact whole-protein family identifiers for Sir3, Sir4, Taz1 and Esc1.
KNOWLEDGE_GAP (OPEN): Resolve condition-dependent central versus peripheral hyperclusters without assigning one universal position.
KNOWLEDGE_GAP (OPEN): Review the full published 2026 Esc1 study when accessible.
CURATION_TODO (RESOLVED): Separate required factors in specific assays from universal component necessity.
CURATION_TODO (RESOLVED): Do not import whole regulatory complexes, markers or tethering diagrams as focus composition.
KNOWLEDGE_GAP (OPEN): Resolve survival effects without equating grouping, silencing and envelope attachment.
CURATION_TODO (RESOLVED): Keep transcriptional transitions separate from hypercluster dynamics.
CURATION_TODO (RESOLVED): Keep experimental taxon, microscopy and morphology scope explicit.
CURATION_TODO (RESOLVED): Separate article CC BY permission from the accompanying data waiver.

More images

Image (not hosted — OTHER): PMC4907721.1 F1

Figure 1 combines telomeric FISH, Sir2/Sir3/Rap1 fluorescence and a time course comparing cycling and quiescent budding yeast. Sir2-only nucleolar foci are distinct from telomeric foci; the FISH procedure loses nucleolar Sir2 signal. Source bars are 2 micrometers. OTHER · Saccharomyces cerevisiae (NCBITaxon:4932) · Damien Laporte, Fabien Courtout, Sylvain Tollis, Isabelle Sagot; CC BY-NC-SA 3.0, via PubMed Central. · OTHER · source: PMC PMC4907721.1 F1 · DOI:10.1091/mbc.E16-01-0069

Image (not hosted — CC_BY_NC_4_0): PMC7102995.1 F1

Figure 1 compares Taz1-GFP telomere foci and Amo1-RFP nuclear envelope in vegetative and nitrogen-starved fission yeast, with focus counts and positional analysis. Panel A is an anchoring model, not direct imaging of all depicted proteins; B includes 5 and 3 micrometer bars. OTHER · Schizosaccharomyces pombe (NCBITaxon:4896) · Laetitia Maestroni, Céline Reyes, Mélina Vaurs, Yannick Gachet, Sylvie Tournier, Vincent Géli, Stéphane Coulon; CC BY-NC 4.0, via PubMed Central. · CC_BY_NC_4_0 · source: PMC PMC7102995.1 F1 · DOI:10.1093/nar/gkaa043

Datasets

Guidi et al. 2015 (10.6084/m9.figshare.1505174.v1) · FIGSHARE · STRUCTURAL_IMAGING
Organism: Saccharomyces cerevisiae
Native Figshare API metadata checked on 2026-10-05: version 1, CC BY 4.0, raw-image ZIP 150807_Guidi_et_al_2015_raw_images.zip, 46976914 bytes. Whole-field Z-stacks and projections differ from cropped publication panels. The ZIP was not downloaded or independently reanalyzed.
Saccharomyces cerevisiae (PRJNA291473) · NCBI_BIOPROJECT · GENOMICS
Organism: Saccharomyces cerevisiae
Primary-paper data availability and native ENA project XML checked; secondary accession SRP062308. No raw reads were downloaded and no independent contact-map reconstruction was performed.
Spatial reorganization of telomeres in long-lived quiescent cells (GSE71273) · NCBI_GEO · GENOMICS
Organism: Saccharomyces cerevisiae · Platform: ChIP-chip
Native GEO series metadata checked on 2026-10-05: four samples, duplicate comparisons, GPL4131; this is not a transcriptomics assay. Its project PRJNA290776 is distinct from chromosome-conformation project PRJNA291473. Raw arrays were not downloaded or reanalyzed.

Evidence

DOI:10.1186/s13059-015-0766-2 Guidi et al. 2015, PMID 26399229; native PMC4581094.1 Results, Discussion and relevant Methods read. Density purification, microscopy, 3C/Hi-C and chronological-survival assays.
DOI:10.1091/mbc.E16-01-0069 Laporte et al. 2016, PMID 27122604; native PMC4907721.1 Results, Discussion and relevant Methods read. FISH, tagged proteins, positioning, chromatin perturbations and refeeding assays.
DOI:10.1093/nar/gkaa043 Maestroni et al. 2020, PMID 31980821; native PMC7102995.1 Results, Discussion and relevant Methods read. Nitrogen-starved fission yeast; clustering, attachment, telomere erosion and TERRA accumulation are distinguished.
DOI:10.1101/gr.279874.124 Baquero Perez et al. 2025, PMID 40796281; native PMC12487827.1 clustering-related Results and Methods read. Transcriptional shutdown and reactivation are separable from cluster formation and dispersal.
GO:0032993 Native protein-DNA complex definition is broader than the multi-chromosome quiescent assembly.
GO:0005634 Native nucleus term grounds the encompassing compartment.
GO:0000781 — chromosome, telomeric region Native chromosome, telomeric region term denotes a constituent chromosome-end region, not the whole hypercluster.
GO:0099115 — chromosome, subtelomeric region Native chromosome, subtelomeric region term denotes adjacent chromatin participating in the assembly.

Curation history

2026-10-05T17:46:33Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-05T17:49:23Z codex · EXPANDED_RECORD — Added twelve component classes, nine verified protein examples, species-scoped mechanisms, three dataset links, one hosted and two link-only inspected figures, and explicit evidence conflicts and access limits.

Source: data/structures/other/quiescent_telomere_hypercluster.yaml