G-Quadruplex structural motifs modulate protein-RNA interactions within the transcriptome
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE284272 | GEO | 2025/09/06
REPOSITORIES: GEO
Similar Datasets
Project description:Four-stranded G-quadruplex (G4) structures form guanine-rich tracts, but their role in RNA biology remains poorly defined. Herein, we first delineate the presence of endogenous RNA G4s in the human cellular transcriptome by proxy of their binding to interacting proteins, DHX36, GRSF1 and DDX3X. We then demonstrate that a sub-population of these RNA G4s are reliably detected as folded structures in cross-linked cellular lysates using the G4 structure-specific antibody BG4. The 5' UTRs of protein-coding mRNAs show significant enrichment in such folded RNA G4s, particularly within mRNA for ribosomal proteins. As G4s in ribosomal mRNA are evolutionarily conserved in higher vertebrates this points to a common mode for translational co-regulation mediated by RNA G4 structures. Supporting this we find that G4-stabilising small molecules inhibit the translation of ribosomal protein mRNA and significantly down-regulate cellular translation.
2021-11-10 | GSE154570 | GEO
Project description:Four stranded DNA G-quadruplex (G4) structures are common features of the human genome that are primarily found in active promoters associated with elevated transcription. Here, we explore the relationship between the folding of G4s in promoters, transcription and chromatin state. Transcriptional inhibition by DRB or by triptolide reveals that promoter G4 formation, as assessed G4 ChIP-seq, is not reliant on transcriptional activity. Establishing a link between G4 formation and chromatin accessibility, we demonstrate that chromatin compaction leads to loss of promoter G4s accompanied by a corresponding loss of RNA polymerase II (Pol II). Furthermore, pre-treatment of cells with a G4-stabilising ligand can mitigate Pol II loss at promoters induced by chromatin compaction. Overall, our findings show that G4 formation is fostered in accessible chromatin and does not require active transcription. Furthermore, our findings suggest that G4s have a role to recruit Pol II to promote transcription.
2021-03-31 | GSE162299 | 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
Project description:G-quadruplexes (G4s) are four-stranded nucleic acid structures abundant at gene promoters. They can adopt several distinctive conformations. G4s have been shown to form in the herpes simplex virus-1 (HSV-1) genome during its viral cycle. Here by cross-linking/pull-down assay we identified ICP4, the major HSV-1 transcription factor, as the protein that most efficiently interacts with viral G4s during infection. ICP4 specific and direct binding and unfolding of parallel G4s, including those present in HSV-1 immediate early gene promoters, induced transcription in vitro and in infected cells. This mechanism was also exploited by ICP4 to promote its own transcription. Proximity ligation assay allowed visualization of G4-protein interaction at the single selected G4 in cells. G4 ligands inhibited ICP4 binding to G4s. Our results indicate the existence of a well-defined G4-viral protein network that regulates the productive HSV-1 cycle. They also point to G4s as elements that recruit transcription factors to activate transcription in cells.
2021-09-10 | PXD024743 | Pride
Project description:DNA G-quadruplexes (G4s) are non-canonical secondary structures formed in Guanine-rich DNA sequences and recent studies demonstrate G4s play important roles in modulating multiple biological processes through a variety of gene regulatory mechanisms. Emerging G4 profiling permit global mapping of endogenous G4 formation. Here in this study, we map the G4 landscapes in skeletal muscle stem cells (MuSCs) which are essential for injury induced muscle regeneration. Throughout the myogenic lineage progression of MuSCs from quiescent to activated to differentiated cells, we uncover dynamic endogenous G4 formation with a pronounced G4 induction when MuSCs become activated and proliferating. We further demonstrate that G4 induction promotes MuSC activation thus the regeneration process. Mechanistically, we found that promoter associated G4s regulate gene transcription in through facilitating DNA looping. Furthermore, we found that G4 sites are enriched for transcription factor (TF) binding events in activated MuSCs and MAX binds to G4 structures to promote E-P looping and gene transcription. The above uncovered global regulatory function/mechanism are further dissected on the paradigm of CCNE1 promoter demonstrating CCNE1 is a bona fid G4/MAX regulatory target in activated MuSCs. Altogether, our findings for the first time demonstrate the prevalent and dynamic formation of G4s in MuSCs and the mechanistic role of G4s in promoting gene expression and MuSC activation/proliferation.
2025-08-20 | GSE289448 | GEO
Project description:DNA G-quadruplexes (G4s) are non-canonical secondary structures formed in Guanine-rich DNA sequences and recent studies demonstrate G4s play important roles in modulating multiple biological processes through a variety of gene regulatory mechanisms. Emerging G4 profiling permit global mapping of endogenous G4 formation. Here in this study, we map the G4 landscapes in skeletal muscle stem cells (MuSCs) which are essential for injury induced muscle regeneration. Throughout the myogenic lineage progression of MuSCs from quiescent to activated to differentiated cells, we uncover dynamic endogenous G4 formation with a pronounced G4 induction when MuSCs become activated and proliferating. We further demonstrate that G4 induction promotes MuSC activation thus the regeneration process. Mechanistically, we found that promoter associated G4s regulate gene transcription in through facilitating DNA looping. Furthermore, we found that G4 sites are enriched for transcription factor (TF) binding events in activated MuSCs and MAX binds to G4 structures to promote E-P looping and gene transcription. The above uncovered global regulatory function/mechanism are further dissected on the paradigm of CCNE1 promoter demonstrating CCNE1 is a bona fid G4/MAX regulatory target in activated MuSCs. Altogether, our findings for the first time demonstrate the prevalent and dynamic formation of G4s in MuSCs and the mechanistic role of G4s in promoting gene expression and MuSC activation/proliferation.
2025-08-20 | GSE289446 | GEO
Project description:DNA G-quadruplexes (G4s) are non-canonical secondary structures formed in Guanine-rich DNA sequences and recent studies demonstrate G4s play important roles in modulating multiple biological processes through a variety of gene regulatory mechanisms. Emerging G4 profiling permit global mapping of endogenous G4 formation. Here in this study, we map the G4 landscapes in skeletal muscle stem cells (MuSCs) which are essential for injury induced muscle regeneration. Throughout the myogenic lineage progression of MuSCs from quiescent to activated to differentiated cells, we uncover dynamic endogenous G4 formation with a pronounced G4 induction when MuSCs become activated and proliferating. We further demonstrate that G4 induction promotes MuSC activation thus the regeneration process. Mechanistically, we found that promoter associated G4s regulate gene transcription in through facilitating DNA looping. Furthermore, we found that G4 sites are enriched for transcription factor (TF) binding events in activated MuSCs and MAX binds to G4 structures to promote E-P looping and gene transcription. The above uncovered global regulatory function/mechanism are further dissected on the paradigm of CCNE1 promoter demonstrating CCNE1 is a bona fid G4/MAX regulatory target in activated MuSCs. Altogether, our findings for the first time demonstrate the prevalent and dynamic formation of G4s in MuSCs and the mechanistic role of G4s in promoting gene expression and MuSC activation/proliferation.
2025-08-20 | GSE289445 | GEO
Project description:DNA G-quadruplexes (G4s) are non-canonical secondary structures formed in Guanine-rich DNA sequences and recent studies demonstrate G4s play important roles in modulating multiple biological processes through a variety of gene regulatory mechanisms. Emerging G4 profiling permit global mapping of endogenous G4 formation. Here in this study, we map the G4 landscapes in skeletal muscle stem cells (MuSCs) which are essential for injury induced muscle regeneration. Throughout the myogenic lineage progression of MuSCs from quiescent to activated to differentiated cells, we uncover dynamic endogenous G4 formation with a pronounced G4 induction when MuSCs become activated and proliferating. We further demonstrate that G4 induction promotes MuSC activation thus the regeneration process. Mechanistically, we found that promoter associated G4s regulate gene transcription in through facilitating DNA looping. Furthermore, we found that G4 sites are enriched for transcription factor (TF) binding events in activated MuSCs and MAX binds to G4 structures to promote E-P looping and gene transcription. The above uncovered global regulatory function/mechanism are further dissected on the paradigm of CCNE1 promoter demonstrating CCNE1 is a bona fid G4/MAX regulatory target in activated MuSCs. Altogether, our findings for the first time demonstrate the prevalent and dynamic formation of G4s in MuSCs and the mechanistic role of G4s in promoting gene expression and MuSC activation/proliferation.
2025-08-20 | GSE289449 | 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:G-quadruplex (G4) structures can form in guanine-rich stretches of DNA or RNA and have been found to modulate a variety of cellular processes including replication, transcription, and translation. Most studies on the cellular roles of G4s have focused on eukaryotic systems, with far fewer probing G4s in bacteria. We utilized a chemical-genetic approach to identify genes in Escherichia coli that are important for growth in conditions that stabilize G4s. Our screens reveal translation elongation to be a key process that is impacted by G4 stabilization. Reducing levels of elongation factor Tu or slowing translation elongation with chloramphenicol suppress the effects of G4 stabilization. In contrast, downregulating the levels of certain essential translation termination or ribosome recycling proteins is detrimental to growth in G4-stabilizing conditions. Proteomic and transcriptomic analyses demonstrate that ribosome assembly factors and other proteins involved in translation generally are less abundantly expressed under G4-stabilizing conditions. Taken together, the results suggest that RNA G4s present barriers to E. coli growth in G4-stabilizing conditions and reducing the rate of translation can help compensate for G4-related stress.
2024-08-19 | GSE271718 | GEO