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G-quadruplex stabilization

ABSTRACT: The effect of prolonged G-quadruplex stabilization on the functions of human cells

PROVIDER: PRJEB85998 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR15003677_1.fastq.gz	Fastqsanger.gz
	ERR15003677_2.fastq.gz	Fastqsanger.gz
	ERR15003678_1.fastq.gz	Fastqsanger.gz
	ERR15003678_2.fastq.gz	Fastqsanger.gz
	ERR15003679_1.fastq.gz	Fastqsanger.gz

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Genomic G-Quadruplex folding and unfolding following global DNA demethylation

Project description:We demonstrate that CpG methylation status may impact the genome-wide folding and stabilization of G-Quadruplex in human cancer cells.

2025-02-07 | GSE196282 | GEO

Native G-quadruplexes Stabilization Impairs Transcription Initiation

Project description:G-quadruplexes (G4s) are noncanonical DNA secondary structures formed through the self-association of guanines. They are distributed genome-widely and participate in multiple biological processes including gene transcription, and quadruplex-targeted ligands serve as potential therapeutic agents for DNA-targeted therapies. However, the roles of G-quadruplexes in transcriptional regulation remains elusive. Here, we establish a sensitive G4-CUT&Tag method for genome-wide profiling of native G-quadruplexes with high resolution and specificity. We find that native G-quadruplex signals are cell-type specific and are associated with transcriptional regulatory elements with active epigenetic modifications. Promoter-proximal RNA polymerase II pausing promotes native G-quadruplex formation, oppositely, G-quadruplex stabilization by quadruplex-targeted ligands globally reduces RNA polymerase II occupancy at gene promoters as well as nascent RNA synthesis. Moreover, G-quadruplex stabilization modulates chromatin states and impedes transcription initiation via inhibiting the loading of general transcription factors to promoters.Together, these studies reveal a reciprocal regulation between native G-quadruplex dynamics and gene transcription in the genome, which will deepen our knowledge of G-quadruplex biology towards considering therapeutically targeting G-quadruplexes in human diseases.

2021-07-19 | GSE178668 | GEO

Effect of specific G-quadruplex stabilization on gene expression and chromatin accessibility at gene promoters in Hela cells.

Project description:To investigate specific G-quadruplex stabilization in the regulation of gene expression and chromatin accessibility, we established HeLa cell lines in which each target g-quadruplexes has been stabilized.

2024-05-25 | GSE255625 | GEO

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.

2013-05-08 | E-GEOD-45241 | biostudies-arrayexpress

The effect of G-quadruplex on gene expression by treating S2 cell with different concentration of TMPyP4

Project description:In this study, G-quadruplex ligand TMPyP4 was utilized to treat S2 cell and DMSO was served as control. The stabilization role of TMPyP4 will promote the formation of G-quadruplex and then affect gene expression. Identifying whether the effect is positive or negative is important for our understanding of the functionality of non-coding element.

2024-05-13 | GSE131691 | GEO

Effect of specific G-quadruplex stabilization on gene expression and chromatin accessibility at gene promoters in Hela cells.

Project description:Effect of specific G-quadruplex stabilization on gene expression and chromatin accessibility at gene promoters in Hela cells.

| PRJNA1075785 | ENA

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

2013-05-08 | GSE45241 | GEO

Small molecule-based regulation of gene expression in human astrocytes switching on and off the G-quadruplex control systems

Project description:A great deal of attention is being paid to strategies seeking to uncover the biology of the four-stranded nucleic acid structure G-quadruplex (G4) via their stabilization in cells with G4-specific ligands. The conventional definition of chemical biology implies that a complete assessment of G4 biology can only be achieved by implementing a complementary approach involving destabilization of cellular G4s by ad hoc molecular effectors. We report here on an unprecedented comparison of the cellular consequences of G4 chemical stabilization by pyridostatin (PDS) and destabilization by phenylpyrrolocytosine (PhpC) at both transcriptome- and proteome-wide scales in patient-derived primary human astrocytes. Our results show that the stabilization of G4s by PDS triggers the dysregulation of many cellular circuitries, the most drastic effects originating in downregulation of 354 transcripts and 158 proteins primarily involved in RNA transactions. In contrast, destabilization of G4s by PhpC modulates the G4 landscapes in a far more focused manner with upregulation of 295 proteins, mostly involved in RNA transactions as well, thus mirroring the effects of PDS. Our study is the first of its kind to report the extent of G4-associated cellular circuitries in human cells by systematically pitting the effect of G4 stabilization against destabilization in a direct and unbiased manner.

2025-01-29 | GSE279752 | GEO

Bisquinolinium Compounds Induce Quadruplex-Specific Transcriptome Changes in HeLa S3 Cell Line

Project description:The effect of bisquinolinium compounds PhenDC3 and 360A genome wide gene expression changes modulated via promoter based G-quadruplex (G4) motifs. The total RNA was extracted after treating HeLa S3 cells with 10 ÂµM of no molecule (DMSO), 8979A (control molecule), PhenDC3 (G4 specific molecule) or 360A (G4 specific molecule) for 48 hrs in triplicate.

2012-05-29 | E-GEOD-32170 | biostudies-arrayexpress

RNA-Seq to assess the transcriptional effects of G quadruplex stabilization by the G4 ligand PhenDC3 in HT-1080 cells

Project description:G-quadruplex motifs are frequently located near TSS and in the first introns of transcribed genes. We investigated the role that G4 structures play in transcription by stabilizing G4 DNA with the selective G4 ligand PhenDC3 in the HT-1080 human fibrosarcoma cell line. After treatment of triplicate samples with PhenDC3 or a negative control (DMSO carrier only), we performed RNA-Seq after poly-dT selection to assess changes in gene expression. Heme is an essential cofactor for many enzymes, but free heme is toxic and its levels are tightly regulated. G-quadruplexes bind heme avidly in vitro, raising the possibility that they may sequester heme in vivo. If so, then treatment that displaces heme from quadruplexes is predicted to induce expression of genes involved in iron and heme homeostasis. Here we show that PhenDC3, a G-quadruplex ligand structurally unrelated to heme, displaces quadruplex-bound heme in vitro and alters transcription in cultured human cells, up-regulating genes that support heme degradation and iron homeostasis, and most strikingly causing a 30-fold induction of heme oxidase 1, the key enzyme in heme degradation. We propose that G-quadruplexes sequester heme to protect cells from the pathophysiological consequences of free heme. This identifies a new function for G-quadruplexes and a new mechanism for protection of cells from heme.

2016-01-31 | GSE60630 | GEO

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