Comparative genome-wide transcriptional profile after RTEL1 depletion and G4 stabilisation.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE149850 | GEO | 2021/01/04
REPOSITORIES: GEO
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Project description:Comparative genome-wide transcriptional profile after RTEL1 depletion and G4 stabilisation.
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Project description:Genome-wide characterisation of replication and transcription programs upon G4-stabilisation by PhenDC3
2019-06-01 | GSE126477 | GEO
Project description:Here, we identify that a human DNA helicase RTEL1, which is known to play a role in the maintenance of telomeres by interacting with proteins in the shelterin complex by resolving G4 quadruplexes, is essential for prevention of R-loop accumulation during replication and for MiDAS in mitosis at both CFSs and telomeres. Our findings indicate that RTEL1 plays a genome-wide role in preventing the collapse of replication forks at sites of G-quadruplexes and R-loop formation. Considering cancer cells rely on RTEL1 function to resolve the elevated transcription-replication conflicts caused by oncogene activation, RTEL1 is a potential drug target for cancer therapy.
2020-02-12 | GSE129907 | GEO
Project description:DNA G-quadruplexes (G4s) have been identified as important biological targets for transcriptional, translational, and epigenetic regulation. The stabilisation of G4s with small molecule ligands has emerged as a technique to regulate gene expression and as a potential therapeutic approach for human diseases. Here, we demonstrate that ligand stabilisation of G4s causes altered chromatin accessibility dependant on the targeting specificity of the molecule. In particular, stabilisation of a target G4 using the highly specific GTC365 ligand resulted in differential accessibility of 61 genomic regions, while the broad targeted GQC-05 ligand stabilised many G4s and induced a global shift towards increased accessibility of gene promoter regions. Interestingly, while we observed distinct effects of each ligand on RNA expression levels and the induction of DNA double-stranded breaks, both ligands modified DNA damage response pathways. Our work represents the dual possibility of G4-stabilising ligands for specific or global chromatin modulation via unique targeting characteristics.
2023-06-28 | GSE235953 | GEO
Project description:DNA G-quadruplexes (G4s) have been identified as important biological targets for transcriptional, translational, and epigenetic regulation. The stabilisation of G4s with small molecule ligands has emerged as a technique to regulate gene expression and as a potential therapeutic approach for human diseases. Here, we demonstrate that ligand stabilisation of G4s causes altered chromatin accessibility dependant on the targeting specificity of the molecule. In particular, stabilisation of a target G4 using the highly specific GTC365 ligand resulted in differential accessibility of 61 genomic regions, while the broad targeted GQC-05 ligand stabilised many G4s and induced a global shift towards increased accessibility of gene promoter regions. Interestingly, while we observed distinct effects of each ligand on RNA expression levels and the induction of DNA double-stranded breaks, both ligands modified DNA damage response pathways. Our work represents the dual possibility of G4-stabilising ligands for specific or global chromatin modulation via unique targeting characteristics.
2023-06-28 | GSE235952 | GEO
Project description:Currently, the identification of G4 quadruplexes in vivo depends on a published and widely used G4-ChIP protocol (PMID: 29470465) that uses the anti-G4 antibody to captures the quadruplexes like regular chromatin. This method is challenged by some false positives and false negatives in G4-quadruplex capture. We have developed an antibody capture G4-ChIP (AbC G4-ChIP) method to overcome these challenges. The AbC G4-ChIP achieves (i) minimized in vitro artifacts during the incubation steps, and (ii) capture of G4-quadruplexes which are not protein-bound. We have applied the AbC G4-ChIP to study the regulatory effect of a CGG-repeat binding protein CGGBP1 on G4-quadruplex formation. The AbC G4-ChIP identifies inter-strand G/C-skew as a sequence property associated with CGGBP1-regulated G4-quadruplexes.
2024-03-20 | GSE202456 | GEO
Project description:RTEL1 regulates G4/R-loops to avert replication-transcription collisions
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Project description:Transcriptional gene silencing is an essential mechanism for controlling the expression of genes and transposable elements (TEs) and is commonly associated with high levels of DNA methylation. Thus, release of silencing is frequently observed in mutants for genes involved in DNA methylation maintenance. However, studies in Arabidopsis thaliana have revealed that transcriptional repression of some DNA-methylated genes and TEs also relies on repressors that operate through pathways largely independent of DNA methylation. One such pathway appears linked to DNA replication and DNA repair and mutations in factors involved in these processes such as the polymerases alpha, delta and epsilon destabilize silencing. Here, we isolate a new mutant allele of the helicase REGULATOR OF TELOMERE ELONGATION 1 (RTEL1) gene from a genetic screen for TGS-deficient mutants. RTEL1 is highly conserved among eukaryotes and plays an important role in the resolution of DNA secondary structures during DNA replication. We show that rtel1 causes release of TGS without loss of DNA methylation or global changes in chromatin accessibility. However, many heterochromatic loci show increased levels of DNA methylation and chromatin accessibility in rtel1 mutants. Our findings reveal a function for RTEL1 in maintaining silencing and in preventing DNA hypermethylation of heterochromatin.
2023-07-04 | GSE197614 | GEO
Project description:G-quadruplexes (G4s) are noncanonical DNA secondary structures formed through the self-association of guanines, and they are distributed widely across the genome. G4 participates in multiple biological processes including gene transcription, and G4-targeted ligands serve as potential therapeutic agents for DNA-targeted therapies. However, genome-wide studies of the exact roles of G4s in transcriptional regulation are still lacking. We found that drug-induced promoter-proximal RNA polymerase II pausing promotes nearby G4 formation, and oppositely, G4 stabilization by G4-targeted ligands globally reduces RNA polymerase II occupancy at gene promoters as well as nascent RNA synthesis. To study the underlying mechanisms by which native G4 affects transcriptional regulation, we annealed the biotin-labeled core promoter DNA to form G4s and performed pull-down assays with nuclear extraction proteins in the presence or absence of TMPyP4. Mass spectrometry analysis was performed to identify the interacting proteins with G4-forming core promoter DNA.
2021-07-19 | PXD026830 | Pride
Project description:The identification of DNA G-quadruplexes (G4s) in the genome is important to study different biological processes in which these structures play a role, such as genome rearrangement, transcriptional regulation and DNA replication. G4-seq allowed the high-throughput experimental mapping of G-quadruplexes in the human genome. We developed here an improved version of this method, named G4-seq2, which we applied to generate G-quadruplexes genomic maps for 12 species, selected as important models organism to study development or as pathogens of clinical relevance. Those multi-species maps, publicly available for the community, will allow to further understand the design principle of G-quadruplex formation in genomic context, to study G-quadruplex biology in those model organisms, to predict ligand targeting for therapeutic usage and to design G-quadruplex computational predictors based on genome-wide experimental measurements.
2018-08-01 | GSE110582 | GEO