Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Shelterin and subtelomeric DNA sequences control nucleosome maintenance and genome stability

ABSTRACT: Telomeres and the shelterin complex cap and protect the ends of chromosomes. Telomeres are flanked by the subtelomeric sequences that have also been implicated in telomere regulation, although their role is not well defined. Here we show that, in Schizosaccharomyces pombe, the telomere-associated sequences (TAS) present on most subtelomeres are hyper-recombinogenic, have metastable nucleosomes, and unusual low levels of H3K9 methylation. Ccq1, a subunit of shelterin, protects TAS from nucleosome loss by recruiting the heterochromatic repressor complexes CLRC and SHREC, thereby linking nucleosome stability to gene silencing. Nucleosome instability at TAS is independent of telomeric repeats and can be transmitted to an intrachromosomal locus containing an ectopic TAS fragment, indicating that this is an intrinsic property of the underlying DNA sequence. When telomerase recruitment is compromised in cells lacking Ccq1, DNA sequences present in the TAS promote recombination between chromosomal ends, independent of nucleosome abundance, implying an active function of these sequences in telomere maintenance. We propose that Ccq1 and fragile subtelomeres co-evolved to regulate telomere plasticity by controlling nucleosome occupancy and genome stability.

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE121502 | GEO | 2018/10/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator

Project description:Telomeres constitute the ends of linear chromosomes and together with the shelterin complex form a structure essential for genome maintenance and stability. In addition to the constitutive binding of the shelterin complex, other direct, yet more transient interactions are mediated by the CST complex and HOT1, while subtelomeric variant repeats are recognized by NR2C/F transcription factors. Recently, the Kruppel-like zinc finger protein ZBTB48 has been described as a novel telomere-associated factor in the vertebrate lineage. Here, we show that ZBTB48 binds directly both to telomeric as well as to subtelomeric variant repeat sequences. ZBTB48 is found at telomeres of human cancer cells regardless of the mode of telomere maintenance and it acts as a negative regulator of telomere length. In addition to its telomeric function, we demonstrate through a combination of RNAseq, ChIPseq and expression proteomics experiments that ZBTB48 acts as a transcriptional activator on a small set of target genes, including mitochondrial fission process 1 (MTFP1). This discovery places ZBTB48 at the interface of telomere length regulation, transcriptional control and mitochondrial metabolism.

2017-05-11 | PXD006074 | Pride

ZNF524 directly binds telomeres and supports their integrity via TRF2/RAP1

Project description:Telomeres are nucleoprotein structures at the ends of linear chromosomes. In humans, they consist of TTAGGG repeats, which are bound by dedicated proteins such as the shelterin complex. This complex consists of six proteins (TRF1, TRF2, RAP1, POT1, TPP1 and TIN2) and blocks unwanted DNA damage repair at telomeres, e.g. by suppressing non-homologous end joining (NHEJ) through its subunit TRF2. While shelterin does not work autonomously, additional direct telomere binding proteins have been described to function in a supplementary role. We here describe ZNF524, a zinc finger protein that directly binds to telomeric repeats with nanomolar affinity and reveal the base-specific sequence recognition by co-crystallization with telomeric DNA. ZNF524 localizes to telomeres and specifically maintains the presence of the TRF2/RAP1 subcomplex at telomeres without affecting the other shelterin members. Loss of ZNF524 concomitantly results in an increase in DNA damage signaling and recombination events. Overall, we identified ZNF524 as a direct telomere binding protein and propose that ZNF524 is involved in the maintenance of telomere integrity by promoting TRF2/RAP1 subcomplex binding.

2023-10-21 | PXD024630 | Pride

ZNF524 directly binds telomeres and supports their integrity via TRF2/RAP1

2023-10-22 | PXD031416 | Pride

TEBP-1 and TEBP-2 are double-stranded telomere binders required for fertility

Project description:Telomeres are the ends of linear chromosomes and consist of repetitive double- and single-stranded DNA sequences. Telomeres are bound by dedicated protein complexes, such as shelterin in mammals. In the nematode Caenorhabditis elegans, a comprehensive understanding of the proteins interacting with the telomere sequence is lacking. Here, we harnessed a quantitative proteomics approach to screen for proteins binding to C. elegans telomeres, and identified TEBP-1 and TEBP-2, two paralogs that associate to telomeres in vitro and in vivo. TEBP-1 and TEBP-2 form a telomeric complex with the known single-stranded telomere-binding proteins POT-1, POT-2, and MRT-1. tebp-1 and tebp-2 mutants display strikingly distinct phenotypes: tebp-1 mutants have longer telomeres than wild-type animals, while tebp 2 mutants display shorter telomeres and a mortal germline, a phenotype characterized by transgenerational germline deterioration. Notably, tebp 1;tebp-2 double mutant animals are synthetic sterile, with germlines showing signs of severe mitotic and meiotic arrest. These results define the first telomere-binding complex of C. elegans, including TEBP-1 and TEBP-2, two double-stranded telomere binders required for fertility.

2021-03-09 | PXD019241 | Pride

ZNF524 directly interacts with telomeric DNA and supports telomere integrity

Project description:Telomeres are nucleoprotein structures at the ends of linear chromosomes. In humans, they consist of TTAGGG repeats, which are bound by dedicated proteins such as the shelterin complex. This complex blocks unwanted DNA damage repair at telomeres, e.g. by suppressing non-homologous end joining (NHEJ) through its subunit TRF2. We here describe ZNF524, a zinc finger protein that directly binds telomeric repeats with nanomolar affinity and reveal the base-specific sequence recognition by co-crystallization with telomeric DNA. ZNF524 localizes to telomeres and specifically maintains the presence of the TRF2/RAP1 subcomplex at telomeres without affecting other shelterin members. Loss of ZNF524 concomitantly results in an increase in DNA damage signaling and recombination events. Overall, ZNF524 is a direct telomere-binding protein involved in the maintenance of telomere integrity.

2023-10-21 | PXD043084 | Pride

The shelterin-dependent recruitment of Stn1-Ten1 ensures replication of hard to replicate subtelomeric regions in fission yeast

Project description:Efficient replication of terminal sequences is crucial to maintain telomere stability. In fission yeast, the Taz1 protein, the TRF1-2 homolog, plays a prominent role in telomere replication. We and others have shown that the Stn1-Ten1 (ST) complex fulfills important function in telomeres and subtelomeres maintenance, however its function is not fully understood. Here, we analyzed genome-wide replication dynamics using the polymerase usage sequencing (PuSeq) allowing to assess polymerase usage across the genome. We show that the ST complex and Taz1 are crucial for the replication of the STE2-3 subtelomeric region. Both, the ST complex and Taz1, bind specifically to this region and the function of the ST complex relies on its association with the shelterin complex. Strikingly, when the ST complex is compromised, an HR-based fork restart mechanism becomes necessary to ensure replication of the STE2-3 region. Finally, we demonstrate that the firing of an origin, that is controlled by Rif1, within subtelomeric regions circumvents the replication defect of subtelomeres. Overall, we demonstrate that the ST complex is actively recruited at subtelomeres by the shelterin and this ensures replication of the STE2-3 region which exhibits specific features of a hard-to-replicate region.

2022-07-01 | GSE207082 | GEO

ZBTB10 binds the telomeric variant repeat TTGGGG and interacts with TRF2

Project description:Telomeres are the ends of linear chromosomes and together with the shelterin complex present an essential feature for genome integrity. Vertebrate telomeres usually consist of hexameric TTAGGG repeats, however, in cells that use the alternative lengthening of telomeres (ALT) mechanism, variant repeat sequences are interspersed throughout telomeres. Previously, it was shown that NR2C/F transcription factors bind to TCAGGG variant repeats and contribute to telomere maintenance in ALT cells. While specific binders to other variant repeat sequences have been lacking to date, we here identify ZBTB10 as the first TTGGGG-binding protein and demonstrate direct binding via the two zinc fingers with affinity in the nanomolar range. Concomitantly, ZBTB10 co-localizes with a subset of telomeres in ALT-positive U2OS cells and interacts with TRF2/RAP1 via the N-terminal region of TRF2. Our data establishes ZBTB10 as a novel variant repeat-specific binding protein at ALT telomeres.

2018-12-17 | PXD010672 | Pride

Condensin positioning at telomeres by shelterin proteins drives sister-telomere disjunction in anaphase

Project description:The localization of condensin along chromosomes is crucial for their accurate segregation in anaphase. Condensin is enriched at telomeres but how and for what purpose had remained elusive. Here we show that fission yeast condensin accumulates at telomere repeats through the balancing acts of Taz1, a core component of the shelterin complex that ensures telomeric functions, and Mit1, a nucleosome-remodeler associated with shelterin. We further show that condensin takes part in sister-telomere separation in anaphase, and that this event can be uncoupled from the prior separation of chromosomes arms, implying a telomere-specific separation mechanism. Consistent with a cis-acting process, increasing or decreasing condensin occupancy specifically at telomeres modifies accordingly the efficiency of their separation in anaphase. Genetic evidence suggests that condensin promotes sister-telomere separation by counteracting cohesin. Thus, our results reveal a shelterin-based mechanism that enriches condensin at telomeres to drive in cis their separation during mitosis.

2023-10-02 | GSE196149 | GEO

RNA-Seq of young and senescent cells with empty vector, TRF2 overexpression or LMNB1 downregulation

Project description:Telomeres, the nucleoprotein structures located at the end of eukaryotic DNA, protect chromosomal integrity. These structures undergo changes during development and aging, including length shortening and alterations in the levels of the proteins associated to them called shelterin, all this affecting genome stability as the cells age. However, telomeres also behave as transcriptional regulators acting not only on genes present at subtelomeres but also on more distantly located genes presented throughout the genome. This process is referred as Telomere Position Effect (TPE). Here we set to determine whether telomere shortening in senescent cells impact TPE and senescent cells transcriptome. We also investigate whether TRF2 (a shelterin protein) and Lamin B1 (a member of nuclear lamina) are involved in TPE by doing RNA sequencing of young and senescent cells in which we modulated TRF2 and Lamin B1 expression.

2023-03-02 | GSE180406 | GEO

A cell cycle switch in TRF2 controls t-loop dynamics and DNA secondary structure resolution across the genome

Project description:Telomere end-protection by the shelterin complex prevents DNA damage signalling and promiscuous repair at chromosome ends. Evidence suggests that the 3’ single-stranded telomere end can assemble into a lasso-like t-loop configuration, which has been proposed to safeguard chromosome ends from being recognized as DNA double strand breaks. Mechanisms must also exist to transiently disassemble t-loops to allow faithful telomere replication and to permit telomerase access to the 3’-end to solve the end replication problem. However, the regulation and physiological importance of t-loops in end-protection remains uncertain. Here, we identify a CDK phosphorylation site in the shelterin subunit, TRF2 (Ser365), whose dephosphorylation in S-phase by the PP6C/R3 phosphatase provides a narrow window during which the helicase RTEL1 is able to transiently access and unwind t-loops to facilitate telomere replication. Re-phosphorylation of TRF2 on Ser365 outside of S-phase is required to release RTEL1 from telomeres, which not only protects t-loops from promiscuous unwinding and inappropriate ATM activation, but also counteracts replication conflicts at DNA secondary structures arising within telomeres and across the genome. Hence, a phospho-switch in TRF2 coordinates assembly and disassembly of t-loops during the cell cycle, which protects telomeres from replication stress and an unscheduled DNA damage response.

2019-11-25 | PXD014843 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data