Ontology highlight
ABSTRACT:
PROVIDER: PRJNA851386 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19763930.fastq.gz | Fastqsanger.gz | |||
| SRR19763931.fastq.gz | Fastqsanger.gz | |||
| SRR19763932.fastq.gz | Fastqsanger.gz | |||
| SRR19763933.fastq.gz | Fastqsanger.gz | |||
| SRR19763934.fastq.gz | Fastqsanger.gz |
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Project description:Telomere maintenance is essential for genome stability, and its regulation during the cell cycle remains a critical area of research. Screening for telomerase-interacting proteins is crucial for understanding the biological processes of telomerase maturation, processing, and recruitment. Using PhastID screening with TERT during S-phase, we identify STRBP, a GEMs-associated protein, as a novel regulator of telomerase activity and telomere length. Our data demonstrate that STRBP mediates interaction with telomerase through TERRA, this interaction negatively regulates telomerase activity, thereby limiting telomere elongation. Notably, TERRA levels decrease during S-phase, potentially facilitating the recruitment of telomerase to telomeres and enabling telomere extension.
2025-10-09 | PXD069238 |
Project description:The Rif1 protein negatively regulates telomeric TG repeat length in the budding yeast S. cerevisiae, but how it prevents telomere over-extension is unknown. Rif1 was recently shown to control DNA replication by acting as a Protein Phosphatase 1 (PP1)-targeting subunit. Therefore we investigated whether Rif1 controls telomere length by targeting PP1 activity. We find that a Rif1 mutant that cannot interact with PP1 causes a long-telomere phenotype, similar to that of rif1∆ cells. Compromised PP1 function also causes telomere extension. Tethering PP1 at a specific telomere partially substitutes for Rif1 in limiting TG repeat length, confirming the importance of PP1 in telomere length control. Ablating Rif1-PP1 interaction leads to precocious activation of telomere-proximal replication origins and aberrantly early telomere replication. However, we find that Rif1 still limits telomere length even if nearby replication origins are deleted, indicating that effects of Rif1 on telomere length are not mediated through replication timing. Instead we find that, even at a telomere created after DNA synthesis during a mitotic block, Rif1-PP1 interaction is required to suppress telomere lengthening and prevent inappropriate recruitment of Tel1 kinase. Overall, our results show that Rif1 controls telomere length by recruiting PP1 to directly suppress telomerase-mediated TG repeat lengthening.
2018-02-14 | GSE109241 | GEO
Project description:Aneuploidy represents the most prevalent form of genetic instability found in human embryos and is the leading genetic cause of miscarriage and developmental delay in newborns. Telomere DNA deficiency is associated with genomic instability in somatic cells and may play a role in development of aneuploidy commonly found in female germ cells and human embryos. To test this hypothesis, we developed a method capable of quantifying telomere DNA in parallel with 24-chromosome aneuploidy screening from the same oocyte or embryo biopsy. Aneuploid human polar bodies possessed significantly less telomere DNA than euploid polar bodies from sibling oocytes (-3.07 fold, P=0.016). This indicates that oocytes with telomere DNA deficiency are prone to aneuploidy development during meiosis. Aneuploid embryonic cells also possessed significantly less telomere DNA than euploid embryonic cells at the cleavage stage (-2.60 fold, P=0.002) but not at the blastocyst stage (-1.18 fold, P=0.340). The lack of a significant difference at the blastocyst stage was found to be due to telomere DNA normalization between the cleavage and blastocyst stage of embryogenesis and not due to developmental arrest of embryos with short telomeres. Heterogeneity in telomere length within oocytes may provide an opportunity to improve the treatment of infertility through telomere based selection of oocytes and embryos with reproductive competence.
2011-07-04 | GSE25864 | GEO
Project description:Genetic lesions that reduce telomerase cause a range of incurable diseases including dyskeratosis congenita (DC) and pulmonary fibrosis (PF), and restoring telomere length in these patients would be curative. Ectopic expression of telomerase reverse transcriptase (TERT) risks cellular immortalization, and how to target telomerase in stem cells throughout the body remains unclear. Here we describe a successful screen for small molecules that augment TERC, the non-coding telomerase RNA component, and thereby specifically elongate telomeres in stem cells. PAPD5 is a non-canonical polymerase that oligo-adenylates and destabilizes TERC. Using a high-throughput screen we identify BCH001, a specific PAPD5 inhibitor that decreases TERC 3′- oligo(A) tailing and increases telomerase activity and telomere length by thousands of nucleotides in DC patient induced pluripotent stem cells (iPSCs). BCH001 does not result in immortalization or telomere elongation in somatic cells which lack TERT, establishing a favorable safety profile. When human hematopoietic stem and progenitor cells (HSPCs) engineered by CRISPR-Cas9 to carry PARN mutations that cause DC and PF are xenotransplanted into immunodeficient mice, oral treatment with PAPD5 inhibitors rescues TERC 3′-end maturation and telomere length. Our data demonstrate telomere restoration in human stem cells in vivo using small molecules.
2020-04-21 | GSE144986 | GEO
Project description:ZBTB48 (also known as TZAP) is a transcription factor that has previously been reported to bind to telomeres and act as a negative regulator of telomere length in human cell lines. To explore whether transcription factor activity and telomere length regulation are conserved at the organismal level in vertebrates, we generated a zbtb48-/- zebrafish line via CRISPR‒Cas genome editing. The zbtb48-/- mutants displayed no obvious physical or behavioral abnormalities in the first two generations. We found no statistically significant changes in telomere length in first-generation adults. However, for the gene regulatory aspect of Zbtb48, similar to that in human cancer cell lines, we observed downregulation of mtfp1 at both the mRNA and protein levels in the zbtb48-/- mutants. This suggests that mtfp1 is an evolutionarily conserved regulatory target of Zbtb48. Further investigation of the spatiotemporal expression of zbtb48 in previously published zebrafish data revealed low transcript expression in diverse tissues, except in germline stem cells and gametocytes of the gonads. Notably, Mtfp1 protein downregulation was detected in the ovaries of 40 dpf zbtb48-/- mutants and in the testes of both 40 dpf and 10.5-month-old zbtb48-/- mutants.
2025-01-09 | PXD052763 | Pride
Project description:Dyskeratosis congenita (DKC) is characterized by impaired telomere maintenance and reveals clinical features of premature aging. So far, diagnosis of DKC relies particularly on telomere length screening raising the need for additional biomarkers. In this study, we analysed global DNA methylation (DNAm) profiles of DKC patients. Age-associated DNAm changes were not generally accelerated in DKC. However, we observed significant hypermethylation in the gene for PR domain containing 8 (PRDM8). Notably, the same genomic region revealed hypermethylation in aplastic anemia (AA), and Down syndrome (DS), indicating that there might be an association with premature aging syndromes. Site-specific analysis of DNAm level in PRDM8 with pyrosequencing and MassArray validated aberrant hypermethylation in 14 DKC patients and 27 AA patients. Notably, telomere length was not directly correlated with DNAm in PRDM8, indicating that the two methods are complementary. In conclusion, DNAm at PRDM8 provides a new biomarker to support diagnosis of of AA and DKC.
2016-05-23 | GSE75310 | GEO
Project description:We asked whether telomere shortening impairs differentiation of ESCs into germ cell lineage. Terc-/- ESCs were used to investigate the effects of short telomeres on germ cell specification by in vitro differentiation. Short telomeres greatly reduced induction of PGCLCs from ESCs. Mechanistically, short telomeres resulted in excessive chromatin accessibility, which in turn activated the genes regulated by chromatin. Notably, Fst overexpression reduced BMP-Smad signaling and thus induction of PGCLCs, meanwhile upregulation of MAPK signaling pathway increase somatic lineage differentiation in short telomeres sampels. Moreover, knockin of Terc gene by CRISPR/Cas9 in Terc-/- ESCs restored telomere length and normal gene expression profile, and rescued PGCLC induction, revealing important roles of telomeres in PGC fate decision.
2022-08-31 | GSE157301 | GEO
Project description:CAMPARI2 CRISPR screening for SOCE modulators of ER stress. PC cells were sorted and sequenced for CRISPR whole KO library (De brie). Unsorted, SOrte din LOW PC and LOW PC Tunica treated fro 4hours were analysed.
2023-12-09 | E-MTAB-13548 | biostudies-arrayexpress
Project description:Telomere length heterogeneity in various cell types including stem cells and cancer cells has been recognized. Cell heterogeneity also is found in pluripotent stem cells such as embryonic stem cells (ESCs). The implication and mechanisms underlying the heterogeneity remain to be defined. We have optimized a robust method that can simultaneously measure telomere length coupled with RNA-sequencing analysis (scT&R-seq) in the same human ES cell. Using this method, we show that telomere length varies with pluripotency state. Long telomere hESCs highly express TERF1/TRF1 as well as ZFP42/REX1, PRDM14 and NANOG for naïve pluripotency, in contrast to short telomere hESCs. hESCs express high telomerase activity as expected, and ubiquitously express NOP10 and DKC1, stabilizing components of telomerase complexes, regardless of telomere lengths. Moreover, new candidate genes such as MELK, MSH6 and UBQLN1 cluster with long telomeres and pluripotency network. Notably, short telomere hESCs exhibit higher oxidative phosphorylation primed for lineage differentiation, whereas long telomere hESCs show elevated glycolysis, another key feature for naïve pluripotency. Our data further suggest that telomere length is implicated in metabolism activity and pluripotency state of hESCs. Single cell analysis of telomere and RNA-sequencing can be exploited to further understand the molecular mechanisms of telomere heterogeneity.
2017-11-06 | GSE98644 | GEO
Project description:Telomere DNA length is a complex trait controlled both by multiple loci and environmental factors. Even though the use of telomere DNA length measurement, as a method of assessing stress accumulation and predicting how this will influence survival, is currently being studied in numerous human cohort studies, the importance of telomere length for stress response in ecological studies remains at its infancy. Here, we investigated the telomere changes occurring in the symbiotic coral Stylophora pistillata that has experienced a continuous darkness over 6 months. This stress condition led to the loss of its symbionts, as what is also observed when bleaching occurs in the field at a large-scale due to climate changes and anthropogenic activities, threatening the worldwide reef ecosystem. We found that the continuous darkness condition was associated to telomere DNA length shortening and a downregulation of the expression of the telomere-associated protein POT2. These results pave the way for future studies on the role of telomere in coral stress response and the importance of telomere dysregulation in endangered coral species
2021-09-20 | GSE171268 | GEO