G-quadruplex roles in transcription deciphered by comparative transcriptomic analyses
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PROVIDER: PRJNA551432 | ENA |
REPOSITORIES: ENA
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Project description:G-quadruplexes (G4) are non-canonical nucleic acid structures that can form at certain DNA or RNA guanine-rich sequences. G4 motifs are dispersed throughout the genome and considerably enriched at promoters, where they flank the transcription start site (TSS) and cluster at the 5’ end of the first intron, which suggests potential regulatory roles of quadruplexes in transcription. To improve our understanding of these roles, we have associated gene expression with the frequency of canonical G4 motifs near gene promoters and characterized perturbations caused by treatment with three G-quadruplex ligands, Pyridostatin and the two bisquinolinium compounds PhenDC3 and PhenDC6. We show that enrichment of G4 motifs characterizes the most actively transcribed genes, challenging the notion that quadruplexes chiefly exert negative regulation by blocking progress of RNA polymerase. G4 ligand-treatment altered splicing of transcripts at genes enriched for G4 motifs at the 5’-end of intron 1, suggesting that G-quadruplexes in the pre-mRNA can regulate splicing. Furthermore, our analysis also revealed some of the effects of G4 ligand treatment that likely reflect quadruplex-dependent replication stress leading to the induction of transcriptional signatures compatible with impaired cell cycle progression. Collectively, our results support the view that G-quadruplexes typically function as positive regulators of transcription, suggesting that quadruplexes may stabilize promoter architecture to enable efficient transcription. This analysis provides strong support for function of quadruplexes near the promoter as regulators of transcription and splicing.
2020-11-02 | GSE133419 | GEO
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
Project description:In this study we discover proteins that bind to G4 quadruplex DNA structure. We use modified c-myc quadruplex as a bait, and compare it to the control bait - T15 oligo. We use spectral counts and G-test to determine significant binders. T15 and G4 datafiles are uploaded
2016-07-07 | PXD003501 | Pride
Project description:Genome-wide analyses reveal widespread roles for Spt5 in sense and antisense transcription
| PRJNA336474 | ENA
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.
2013-05-08 | GSE45241 | GEO
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 µM 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
Project description:A new group of G-quadruplex binder, cyclic anthraquinone derivative which named cAQ-mBen was developed for G-quadruplex specific recognition. We used RNA-Seq to explore the effect of cAQ-mBen and anthraquinone derivative which named AQ-ac on the whole-transcriptome profiles of tumor cell line SAS.
2023-06-28 | GSE223310 | GEO
Project description:RNA-binding proteins are important regulators of RNA biogenesis and function, and recent work shows that chromatin- and RNA-binding proteins can have regulatory roles in transcription. Several approaches have been developed to predict RNA-binding proteins and to identify them experimentally at large scale, including binding to structural elements as G-quadruplexes. Here, we show that the histone lysine demethylase protein KDM5 can bind to RNA through interaction with G-quadruplexes with high affinity despite neither being categorized as an RNA-binding protein nor identified as a G-quadruplex binding protein across numerous experimental large-scale and computational studies. In addition to characterizing the KDM5 G-quadruplex interaction we show that RNA is directly involved in the formation of KDM5-containing protein complexes. Computational predictions and comparison to other ARID domain containing proteins suggest that the ARID domain is directly interacting with both DNA and RNA across several proteins. Our work highlights that non-canonical aspects of RNA-binding proteins are present, and that G-quadruplex RNA-binding could provide a regulatory mechanism for chromatin-binding proteins with impact on transcription through linking protein complexes within the cell.
2024-04-11 | PXD050767 | Pride
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
Project description:We analyze the contribution of ATRX, DAXX and HIRA to the chromatin accessibility at G-quadruplex in mESC We analyze the contribution of ATRX and ESET to the chromatin accessibility at G-quadruplex in mESC
2021-05-17 | GSE151053 | GEO