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Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes [CUT&Tag]

ABSTRACT: Telomeres, TTAGGGn DNA repeat sequences located at the ends of eukaryotic chromosomes, play a pivotal role in ageing and are targets of DNA damage and DNA damage response. Although short telomeres have been implicated in heart failure, little is known about the role of telomeres in cardiomyocytes.To fill this gap in knowledge, we studied myocardial ageing in the form of telomere lengths under isogenic background.

ORGANISM(S): Homo sapiens

PROVIDER: GSE230455 | GEO | 2023/12/31

REPOSITORIES: GEO

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Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes [Hi-C]

Project description:Telomeres, TTAGGGn DNA repeat sequences located at the ends of eukaryotic chromosomes, play a pivotal role in ageing and are targets of DNA damage and DNA damage response. Although short telomeres have been implicated in heart failure, little is known about the role of telomeres in cardiomyocytes.To fill this gap in knowledge, we studied myocardial ageing in the form of telomere lengths under isogenic background.

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Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-31 | GSE217703 | GEO

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.

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Project description:Pt-ttpy (tolyl terpyridin-Pt complex) covalently binds to G-quadruplex (G4) structures in vitro and to telomeres in cellulo via its Pt moiety. Here, we identified its targets in the human genome, in comparison to Pt-tpy, its derivative without G4 affinity, and cisplatin. Pt-ttpy, but not Pt-tpy, induces the release of the shelterin protein TRF2 from telomeres concomitantly to the formation of DNA damage foci at telomeres but also at other chromosomal locations. -H2AX chromatin immunoprecipitation (ChIP-seq) after treatment with Pt-ttpy or cisplatin revealed accumulation in G- and A-rich tandemly repeated sequences, but not particularly in potential G4 forming sequences. Collectively, Pt-ttpy presents dual targeting efficiency on DNA, by inducing telomere dysfunction and genomic DNA damage at specific loci.

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