Telomeres expand sphere of influence: emerging molecular impact of telomeres in non-telomeric functions

Vinayagamurthy, Soujanya; Bagri, Sulochana; Mergny, Jean‐Louis; Chowdhury, Shantanu

doi:10.1016/j.tig.2022.10.002

Cited by 11 publications

(6 citation statements)

References 138 publications

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“…2d–i ). In addition, recent reports suggest that telomeres can affect distant as well as nearby chromatins 35 , 36 . This may explain the change in expression of retrotransposons distant from telomeres.…”

Section: Resultsmentioning

confidence: 99%

Critically short telomeres derepress retrotransposons to promote genome instability in embryonic stem cells

Zhao

Yin

et al. 2023

Cell Discov

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Telomeres, at the ends of chromosomes, protect chromosomes from fusion and preserve genomic stability. However, the molecular mechanisms underlying telomere attrition-induced genome instability remain to be understood. We systematically analyzed the expression of retrotransposons and performed genomic sequencing of different cell and tissue types with telomeres of varying lengths due to telomerase deficiency. We found that critically short telomeres altered retrotransposon activity to promote genomic instability in mouse embryonic stem cells, as evidenced by elevated numbers of single nucleotide variants, indels and copy number variations (CNVs). Transpositions of retrotransposons such as LINE1 resulting from the short telomeres can also be found in these genomes with elevated number of mutations and CNVs. Retrotransposon activation is linked to increased chromatin accessibility, and reduced heterochromatin abundance correlates with short telomeres. Re-elongation of telomeres upon recovery of telomerase partly represses retrotransposons and heterochromatin accumulation. Together, our findings suggest a potential mechanism by which telomeres maintain genomic stability by suppressing chromatin accessibility and retrotransposon activity.

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Section: Resultsmentioning

confidence: 99%

Critically short telomeres derepress retrotransposons to promote genome instability in embryonic stem cells

Zhao

Yin

et al. 2023

Cell Discov

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“…Studying age-matched cows of varying parities beyond two calves and the role of telomerase is necessary to fully understand the relationship between parturition, cow longevity, and telomere attenuation. Future investigation of the linkage of telomere maintenance with gene expression, health, productivity, and longevity of beef cattle should encompass appropriate tissue-specific analyses, particularly to increase the comprehension of the potential effects of environmental stressors on the intrauterine or epigenetic programming of the three embryonic germ layers of calves [56][57][58][59][60].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Telomere Length in Age-Matched Primiparous and Multiparous Brahman Cows

O’Daniel

Kochan

Long³

et al. 2023

Animals

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Physiological and psychological stressors have been associated with the attrition of telomeres, which are the protective caps of chromosomes. This study compares the telomere length (TL) in 4-year-old Brahman cows grouped by the first parity (n = 8) and the second parity (n = 11). The cows were bled via jugular venipuncture, weighed, and had their body condition scores recorded at Day −28 prior to calving and at Day + 7 and Day + 28 post-calving. The duration of labor (Dlabor) and parturition ease were recorded. The peripheral leukocytes were isolated, the leukocyte blood count with differential was recorded, and the genomic DNA was extracted. The relative quantity of telomere products, which is proportional to the average TL, was determined via multiplex quantitative PCR using the ratio (T/S ratio) of bovine telomere and β-globulin DNA. Standards of the bovine telomere (1012–107 dilution series) and β-globulin (109–104 dilution series) genes were utilized to produce relative copy numbers. The samples were assayed in triplicate and were included if the triplicate Cq difference was less than 0.25 cycles. The parity was the fixed effect, and the random effects included the sire and day repeated with the cow as the subject. Statistical significance was not observed in the leukocyte number or type (p > 0.1). A reduction in the TL of approximately 9225 telomeric copies was found between Parity 1 and Parity 2 (p = 0.02). A trend was found between the TL and Dlabor (p = 0.06). The stress of parturition and raising the first calf of a cow’s life may be responsible for TL attenuation. Parity may be considered a stressor of cow longevity.

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“…Non-telomeric functions have also been attributed to TERRA, shelterin proteins, constituents of the CST complex, and TERT, collectively referred to as telomere-associated factors (TAFs). These proteins have been found to intricately modulate the transcriptional activity of critical genes dispersed along the length of the human genome [ 96 ]. Additionally, the core components of telomerase have demonstrated functions beyond their telomeric roles across diverse organisms and cell lineages, although the primary focus has been on TERT (as reviewed in [ 97 , 98 ]).…”

Section: Discussionmentioning

confidence: 99%

Global Gene Expression of Post-Senescent Telomerase-Negative ter1Δ Strain of Ustilago maydis

Sanpedro-Luna,

Vega-Alvarado,

Vázquez-Cruz

et al. 2023

JoF

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We analyzed the global expression patterns of telomerase-negative mutants from haploid cells of Ustilago maydis to identify the gene network required for cell survival in the absence of telomerase. Mutations in either of the telomerase core subunits (trt1 and ter1) of the dimorphic fungus U. maydis cause deficiencies in teliospore formation. We report the global transcriptome analysis of two ter1Δ survivor strains of U. maydis, revealing the deregulation of telomerase-deleted responses (TDR) genes, such as DNA-damage response, stress response, cell cycle, subtelomeric, and proximal telomere genes. Other differentially expressed genes (DEGs) found in the ter1Δ survivor strains were related to pathogenic lifestyle factors, plant–pathogen crosstalk, iron uptake, meiosis, and melanin synthesis. The two ter1Δ survivors were phenotypically comparable, yet DEGs were identified when comparing these strains. Our findings suggest that teliospore formation in U. maydis is controlled by key pathogenic lifestyle and meiosis genes.

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Telomeres expand sphere of influence: emerging molecular impact of telomeres in non-telomeric functions

Cited by 11 publications

References 138 publications

Critically short telomeres derepress retrotransposons to promote genome instability in embryonic stem cells

Critically short telomeres derepress retrotransposons to promote genome instability in embryonic stem cells

Comparison of Telomere Length in Age-Matched Primiparous and Multiparous Brahman Cows

Global Gene Expression of Post-Senescent Telomerase-Negative ter1Δ Strain of Ustilago maydis

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