G-quadruplex structures regulate long-range transcriptional reprogramming to promote drug resistance in ovarian cancer [ATAC-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE279495 | GEO | 2025/06/06
REPOSITORIES: GEO
Similar Datasets
Project description: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.
2025-06-06 | GSE279497 | GEO
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.
2025-06-06 | GSE279501 | GEO
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.
2025-06-06 | GSE279641 | GEO
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
2012-10-12 | E-GEOD-41499 | biostudies-arrayexpress
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).
2012-10-12 | GSE41499 | GEO
Project description:Changes in chromatin organization are associated with resistance to anti-cancer drugs, such as platinum-based chemotherapy used as the primary treatment of ovarian cancer. We have examined the genomic distribution of chromatin accessibility changes, and relationship to gene expression changes, occurring during acquisition of resistance in vivo of high grade serous ovarian cancer (HGSOC) patients and whether this associates with genomic DNA damage distribution. Using matched chemo-sensitive and chemo-resistant ovarian cell lines isolated from HGSOC patients before and following acquisition of clinical resistance to platinum-based chemotherapy, we have examined the relationship between chromatin accessibility by ATAC-seq, platinum-DNA adduct distribution by Pt-Exo-seq and gene expression by RNA-seq. We have correlated chromatin changes between the lines at gene promoters, CpG islands, enhancer sequences and other genomic regions with changes in gene expression and platinum-DNA adduct distribution. We observe chromatin conformation differences following acquisition of platinum-resistance, with the HGSOC resistant lines clustering together, separately from their respective sensitive counterparts. Resistant lines show altered chromatin accessibility at intergenic regions, but less so at gene promoters. Super-enhancers, as defined by clusters of cis-regulatory elements, at these intergenic regions show chromatin changes that are associated with altered expression of linked genes, with enrichment for genes involved in the Fanconi anemia/BRCA DNA damage response pathway. Genome-wide distribution of platinum adducts associates with the chromatin changes and distinguish sensitive from resistant lines. Regions incurring fewer platinum-adducts showed a significant reduction in accessibility the resistant HGSOC cell line PEO4 compared to the sensitive PEO1 counterpart. Surprisingly, regions showing increased damage in PEO4 had an even greater reduction in accessibility. In the resistant line, we observe fewer adducts around gene promoters and more adducts at intergenic regions. In cell lines derived from patients following acquisition of clinical resistance to platinum-based chemotherapy, chromatin changes at super-enhancers correlate with gene expression changes in DNA repair pathways known to influence platinum sensitivity. Although cisplatin is a relatively non-specific DNA damaging agent, there are consistent differences in distribution of adducts between the matched sensitive and resistant ovarian cell lines, which is independent of the overall level of adducts formed.
2021-03-27 | GSE149146 | GEO
Project description:Changes in chromatin organization are associated with resistance to anti-cancer drugs, such as platinum-based chemotherapy used as the primary treatment of ovarian cancer. We have examined the genomic distribution of chromatin accessibility changes, and relationship to gene expression changes, occurring during acquisition of resistance in vivo of high grade serous ovarian cancer (HGSOC) patients and whether this associates with genomic DNA damage distribution. Using matched chemo-sensitive and chemo-resistant ovarian cell lines isolated from HGSOC patients before and following acquisition of clinical resistance to platinum-based chemotherapy, we have examined the relationship between chromatin accessibility by ATAC-seq, platinum-DNA adduct distribution by Pt-Exo-seq and gene expression by RNA-seq. We have correlated chromatin changes between the lines at gene promoters, CpG islands, enhancer sequences and other genomic regions with changes in gene expression and platinum-DNA adduct distribution. We observe chromatin conformation differences following acquisition of platinum-resistance, with the HGSOC resistant lines clustering together, separately from their respective sensitive counterparts. Resistant lines show altered chromatin accessibility at intergenic regions, but less so at gene promoters. Super-enhancers, as defined by clusters of cis-regulatory elements, at these intergenic regions show chromatin changes that are associated with altered expression of linked genes, with enrichment for genes involved in the Fanconi anemia/BRCA DNA damage response pathway. Genome-wide distribution of platinum adducts associates with the chromatin changes and distinguish sensitive from resistant lines. Regions incurring fewer platinum-adducts showed a significant reduction in accessibility the resistant HGSOC cell line PEO4 compared to the sensitive PEO1 counterpart. Surprisingly, regions showing increased damage in PEO4 had an even greater reduction in accessibility. In the resistant line, we observe fewer adducts around gene promoters and more adducts at intergenic regions. In cell lines derived from patients following acquisition of clinical resistance to platinum-based chemotherapy, chromatin changes at super-enhancers correlate with gene expression changes in DNA repair pathways known to influence platinum sensitivity. Although cisplatin is a relatively non-specific DNA damaging agent, there are consistent differences in distribution of adducts between the matched sensitive and resistant ovarian cell lines, which is independent of the overall level of adducts formed.
2021-03-27 | GSE149145 | GEO
Project description:Changes in chromatin organization are associated with resistance to anti-cancer drugs, such as platinum-based chemotherapy used as the primary treatment of ovarian cancer. We have examined the genomic distribution of chromatin accessibility changes, and relationship to gene expression changes, occurring during acquisition of resistance in vivo of high grade serous ovarian cancer (HGSOC) patients and whether this associates with genomic DNA damage distribution. Using matched chemo-sensitive and chemo-resistant ovarian cell lines isolated from HGSOC patients before and following acquisition of clinical resistance to platinum-based chemotherapy, we have examined the relationship between chromatin accessibility by ATAC-seq, platinum-DNA adduct distribution by Pt-Exo-seq and gene expression by RNA-seq. We have correlated chromatin changes between the lines at gene promoters, CpG islands, enhancer sequences and other genomic regions with changes in gene expression and platinum-DNA adduct distribution. We observe chromatin conformation differences following acquisition of platinum-resistance, with the HGSOC resistant lines clustering together, separately from their respective sensitive counterparts. Resistant lines show altered chromatin accessibility at intergenic regions, but less so at gene promoters. Super-enhancers, as defined by clusters of cis-regulatory elements, at these intergenic regions show chromatin changes that are associated with altered expression of linked genes, with enrichment for genes involved in the Fanconi anemia/BRCA DNA damage response pathway. Genome-wide distribution of platinum adducts associates with the chromatin changes and distinguish sensitive from resistant lines. Regions incurring fewer platinum-adducts showed a significant reduction in accessibility the resistant HGSOC cell line PEO4 compared to the sensitive PEO1 counterpart. Surprisingly, regions showing increased damage in PEO4 had an even greater reduction in accessibility. In the resistant line, we observe fewer adducts around gene promoters and more adducts at intergenic regions. In cell lines derived from patients following acquisition of clinical resistance to platinum-based chemotherapy, chromatin changes at super-enhancers correlate with gene expression changes in DNA repair pathways known to influence platinum sensitivity. Although cisplatin is a relatively non-specific DNA damaging agent, there are consistent differences in distribution of adducts between the matched sensitive and resistant ovarian cell lines, which is independent of the overall level of adducts formed.
2021-03-27 | GSE147645 | GEO
Project description:DNA secondary structures are important for fundamental genome functions such as transcription and replication1. The G-quadruplex (G4) structural motif has been linked to gene regulation2,3 and genome instability4,5 and may be important to cancer development and other diseases6-8. Recently, ~700,000 discrete G4s have been observed in naked human single-stranded genomic DNA using G4-seq, a high-throughput sequencing technique that detects structural features in vitro.9 It is of vital importance to investigate G4 structures within an endogenous chromatin context, which until now remained elusive10,11. Herein, we address this via the development of G4 ChIP-seq, an antibody-based G4 chromatin immunoprecipitation and high-throughput sequencing approach. We identified ~10,000 endogenous G4 structures and show that G4s are predominantly seen in regulatory, nucleosome-depleted, chromatin regions. G4s were enriched in the promoters and 5âUTR regions of highly transcribed genes, particularly in genes related to cancer and in somatic copy number amplifications, such as MYC. Reorganization of the chromatin landscape using a histone deacetylase inhibitor, resulted in de novo G4 formation in new and more prominent regulatory, nucleosome-depleted regions associated with increased transcriptional output. Our findings suggest a striking relationship between promoter nucleosome-depleted regions, G4 formation and elevated transcriptional activity. Comparison between normal human epidermal keratinocytes and their immortalized counterparts revealed a ï¾7-fold greater G4 abundance in immortalized cells, of which 80 % were found in regulatory, nucleosome-depleted regions common to both cell types. Consequently, cells exhibiting more G4s displayed significantly increased transcriptional output and were more sensitive to growth inhibition by a small molecule G4 ligand. Overall, our results provide new mechanistic insights into where and when DNA adopts G4 structure in vivo. Our findings show for the first time that regulatory, nucleosome-depleted chromatin and transcriptional states predominantly shape the endogenous G4 DNA landscape. Two cell lines, treated with entinostat or untreated, analyzed to detect gene expression differences, presence of G-Qudruplexes and chromatin state. Each combination of conditions replicated in duplicates or triplicates.
2016-08-05 | E-GEOD-76688 | biostudies-arrayexpress