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G-quadruplex structures regulate long-range transcriptional reprogramming to promote drug resistance in ovarian cancer [ChIP-seq]

ABSTRACT: G-quadruplex ChIP-seq has been performed to establish genomic maps of G-quadruplex structures in chemotherapy sensitive (PEO1) and chemotherapy resistant (PEO4) ovarian cancer cell lines to uncover how the changes in G-quadruplex landscape may contribute to the development of chemotherapy resistance for the first time.

ORGANISM(S): Homo sapiens

PROVIDER: GSE279497 | GEO | 2025/06/06

REPOSITORIES: GEO

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G-quadruplex structures regulate long-range transcriptional reprogramming to promote drug resistance in ovarian cancer [CUT&Tag]

Project description:Enhancers are regulatory elements of the genome involved in transcriptional regulation and reprogramming. Similarly, we propose that secondary DNA structures termed G-quadruplexes could also be impacting transcription in an enhancer based way via long-range interactions to bring together regulatory elements of the genome. In this study, we map G-quadruplex structures and h3k27ac enhancer marks in a paired ovarian cancer cell line; PEO1 and PEO4. We endeavour to use these findings to help link the transcriptional function of G-quadruplexes with enchancer in chemotherapy sensitive (PEO1) and chemotherapy resistant (PEO4) ovarian cancer cells.

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G-quadruplex structures regulate long-range transcriptional reprogramming to promote drug resistance in ovarian cancer [RNA-seq]

Project description:G-quadruplexes are secondary DNA structures which have been shown to have an impact on gene transcription via a variety of mechanisms, In this study we generate RNA-seq data of wildtype chemotherpay sensitive (PEO1 A) and chemostherapy resistant (PEO4 A) ovarian cancer cells to intersect with G-quadruplex mapping data to assess how transcription is impacted by G-quadruplex formation. In another variation of the PEO1/4 cell line, in which the PEO1 B cell line has a reversion mutation to reinstate BRCA2, we used the G-quadruplex stabilising molecule pyridostatin (PDS) to treat PEO1 B and its counterpart PEO4 B for either 0, 2 or 6 hours to see how stabilising G-quadruplexes effects gene expression in a temporal manner.

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G-quadruplex structures regulate long-range transcriptional reprogramming to promote drug resistance in ovarian cancer [ATAC-seq]

Project description:Chromatin accessibilty is a key regulator of gene expression. In this study we aim to map accessible chromatin regions in both chemotherapy sensitive (PEO1) and chemotherapy resistant (PEO4) ovarian cancer cell lines, to intersect with RNA-seq data to see how chromatin architecture changes and impacts gene expression between the two cell lines.

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Expression profiling of ovarian cancer cell lines

Project description:Paired platinum-sensitive & platinum-resistant cell lines PEO1 and PEO4 (respectively) were derived from the same patient. Cell line cultures were profiled with the HT-HGU133a GeneChip to investigate chemotherapy resistance related expression of genes marked with different histone modifications in a primary ovarian tumour (clinical data for the primary ovarian tumour is available as Series supplementary file). 4 replicates of each of the PEO1 and PEO4 cell line were profiled using the HT-HGU133a GeneChip

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G-Quadruplex structures are stable and detectable in human genomic DNA.

Project description:The G-quadruplex is an alternative DNA structural motif that is considered to be functionally important in the mammalian genome. Herein, we address the hypothesis that G-quadruplex structures can exist within double-stranded genomic DNA using a G-quadruplex-specific probe. An engineered antibody is employed to enrich for DNA containing G-quadruplex structures, followed by deep sequencing to detect and map G-quadruplexes at high resolution in genomic DNA from human breast adenocarcinoma cells. Our high sensitivity structure-based pull-down strategy enables the isolation of genomic DNA fragments bearing a single as well as multiple G-quadruplex structures. Stable G-quadruplex structures are found in sub-telomeres, gene bodies and gene regulatory regions. For a sample of identified target genes, we show that G-quadruplex stabilizing ligands can modulate transcription. These results confirm the existence of G-quadruplex structures and their persistence in human genomic DNA. Four independent libraries have been enriched in DNA G-quadruplex structures using a G-quadruplex-specific probe. One genomic input library was sequenced as control. Deep-sequencing of these libraries allowed the mapping of G-quadruplexes on the genome.

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Profiling DNA G-quadruplex structures at single-cell level

Project description:Single-cell sequencing data uncovers cellular heterogeneity and enables studies of underlying molecular variations within cell population. Here, we adapted CUT&Tag to profile DNA secondary structure G-quadruplexes at single-cell resolution for the first time and single-cell G-quadruplex maps readily distinguished cell types in a mixed population and revealed variable frequency of G-quadruplexes observed in a given sample.

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G-quadruplex structures regulate long-range transcriptional reprogramming to promote drug resistance in ovarian cancer [ChIP-seq]

Project description:G-quadruplex structures regulate long-range transcriptional reprogramming to promote drug resistance in ovarian cancer [ChIP-seq]

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