Thoroughbred Telomere to Telomere with Chromosome Y
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB96086 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Recurrent exertional rhabdomyolysis (RER) develops in 5-10% of Thoroughbred racehorses. High-stress environments, nervous temperament, and diet influence the presentation of RER. RER-susceptibility is associated with alterations in intramuscular Ca2+ regulation with detrimental effects on mitochondria. Our study aims to determine underlying molecular drivers influencing RER-susceptibility by comparing the muscle proteome of control, RER-susceptible, and RER horses treated with dantrolene. Animals used in this study were Thoroughbred mares in race training between episodes of RER.
2021-01-07 | PXD020100 | Pride
Project description:Telomeres prevent ATM activation by sequestering chromosome termini within telomere loops (t-loops). Mitotic arrest promotes telomere linearity and a localized ATM-dependent telomere DNA damage response (DDR) through an unknown mechanism. Using unbiased interactomics, biochemical screening, molecular biology, and super-resolution imaging, we found that mitotic arrest-dependent (MAD) telomere deprotection requires the combined activities of the Chromosome passenger complex (CPC) on shelterin, and the BLM-TOP3A-RMI1/2 (BTR) complex on t-loops. During mitotic arrest, the CPC component Aurora Kinase B (AURKB) phosphorylated both the TRF1 hinge and TRF2 basic domains. Phosphorylation of the TRF1 hinge domain enhances CPC and TRF1 interaction through the CPC Survivin subunit. Meanwhile, phosphorylation of the TRF2 basic domain promotes telomere linearity, activates a telomere DDR dependent on BTR-mediated double Holliday junction dissolution, and leads to mitotic death. We identify that the TRF2 basic domain functions in mitosis-specific telomere protection and reveal a regulatory role for TRF1 in controlling a physiological ATM-dependent telomere DDR. The data demonstrate that MAD telomere deprotection is a sophisticated active mechanism that exposes telomere ends to signal mitotic stress.
2025-01-28 | PXD043281 | Pride
Project description:Equus caballus strain:thoroughbred Genome sequencing
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Project description:Equus caballus strain:Thoroughbred Genome sequencing
| PRJNA184688 | ENA
Project description:Telomeres have the ability to adopt a lariat conformation and hence, engage in long and short distance intra-chromosome interactions. Budding yeast telomeres were proposed to fold back into subtelomeric regions, but a robust assay to quantitatively characterize this structure has been lacking. Therefore, it is not well understood how the interactions between telomeres and non-telomeric regions are established and regulated. We employ a telomere chromosome conformation capture (Telo-3C)approach to directly analyze telomere folding and its maintenance in S. cerevisiae. We identify the histone modifiers Sir2, Sin3 and Set2 as critical regulators for telomere folding, which suggests that a distinct telomeric chromatin environment is a major requirement for the folding of yeast telomeres. We demonstrate that telomeres are not folded when cells enter replicative senescence, which occurs independently of short telomere length. Indeed, Sir2, Sin3 and Set2 protein levels are decreased during senescence and their absence may thereby prevent telomere folding. Additionally, we show that the homologous recombination machinery, including the Rad51 and Rad52 proteins, as well as the checkpoint component Rad53 are essential for establishing the telomere fold-back structure. This study outlines a method to interrogate telomere-subtelomere interactions at a single unmodified yeast telomere. Using this method, we provide insights into how the spatial arrangement of the chromosome end structure is established and demonstrate that telomere folding is compromised throughout replicative senescence.
2020-11-20 | PXD021085 | Pride
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:Equus caballus breed:Thoroughbred Transcriptome or Gene expression
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Project description:Equus caballus strain:Thoroughbred Transcriptome or Gene expression
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Project description:The budding yeast telomere binding protein Rif1 (Rap1-interacting factor 1) plays an evolutionarily conserved role in the control of DNA replication timing, which operates through an interaction with the PP1 phosphatase. Rif1-PP1 has been proposed to inhibit origin firing by reversing the phosphorylation of key targets involved in replication initiation. However, it is not yet known if Rif1 binds directly to the replication origins that it controls. Here we show that in unperturbed yeast cells Rif1 primarily regulates late-replicating telomere-proximal origins. Using Chromatin Endogenous Cleavage (ChEC)-seq, we find that Rif1 is robustly detected at many late-replicating origins that we identify as targets of its inhibitory action. Abrogation of Rif1 telomere binding, through mutation of its Rap1 binding module, leads to increased Rif1 binding and late origin inhibition elsewhere in the genome. Our results support a model whereby Rif1 inhibits replication initiation by binding directly at origins, most of which are near telomeres, where Rif1 is concentrated through its interaction with telomere-bound Rap1 protein.
2018-04-24 | GSE97953 | GEO
Project description:Cancers harness embryonic programs to evade aging and promote survival. Normally, sequences at chromosome ends called telomeres, shorten with cell division, and function as a countdown clock to limits cell replication. Therefore, a crucial aspect of cancerous transformation is avoiding replicative aging, by activation of telomere repair programs. In mouse embryonic stem cells (mESCs), the transient expression of the gene Zscan4, correlates with chromatin de-condensation and telomere extension. Head and neck cancers reactivate ZSCAN4, which in turn regulates the cancer stem cell (CSCs) phenotype. Our new study reveals a novel role for human ZSCAN4 in facilitating functional histone H3 acetylation at the telomere chromatin. Next-generation sequencing reveals ZSCAN4 enrichment at chromosome ends and its pivotal role in facilitating histone H3 acetylation at telomeres. These epigenetic changes correlate with ZSCAN4-induced telomere elongation, while CRISPR/Cas9 knockout of ZSCAN4 leads to telomere shortening in cancer cells. Our study elucidates the intricate involvement of ZSCAN4 in modulating telomere histone acetylation, and its interaction with telomeric proteins. These findings suggest ZSCAN4 induction as a novel link between cancer stemness and telomere maintenance. Future strategies aimed at blocking ZSCAN4 may provide new therapeutic approaches to effectively target cancer stem cells and limit their replicative lifespan.
2025-04-01 | GSE250470 | GEO