Identification of endogenous G-quadruplexes (G4s) in human, mouse, and pig
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PROVIDER: PRJNA912748 | ENA |
REPOSITORIES: ENA
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Project description:G-quadruplexes (G4s) are non-canonical four-stranded structures and emerge as novel genetic regulatory elements. Endogenous G4s (eG4s) can form quadruplex structures and induce double strand breaking during DNA replication, and thus contributing to genomic instability and genome evolution. Besides, eG4s are closely associated with gene expression regulation, and both their stimulative and repressive roles in the genome have been elucidated. Although functions of several specific G4s have been reported, a systematical identification and characterization of eG4s is still unconducted. Here we applied Cleavage Under Targets and Tagmentation (CUT&Tag) for mapping eG4s across human, mouse, and pig at high resolution and low background. We analyzed their genomics distribution, evolutionary conservation, dynamics, regulation, and impacts on gene expression in a single framework. CUT&Tag using G4-specific antibody, BG4
2025-08-06 | GSE217860 | GEO
Project description:Identification of endogenous G-quadruplexes (G4s) in human, mouse, and pig (CUT&Tag)
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Project description:Identification of endogenous G-quadruplexes (G4s) in human, mouse, and pig (ATAC-Seq)
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Project description:G4s are non-canonical four-stranded structures and emerge as novel genetic regulatory elements. Endogenous G4s (eG4s) can form quadruplex structures and induce double strand breaking during DNA replication, and thus contributing to genomic instability and genome evolution. Besides, eG4s are closely associated with gene expression regulation, and both their stimulative and repressive roles in the genome have been elucidated. Although functions of several specific G4s have been reported, a systematical identification and characterization of eG4s is still unconducted. Here we applied Cleavage Under Targets and Tagmentation (CUT&Tag) for mapping eG4s across human, mouse, and pig at high resolution and low background. We analyzed their genomics distribution, evolutionary conservation, dynamics, regulation, and impacts on gene expression in a single framework. ATAC-seq
2025-08-06 | GSE220209 | GEO
Project description:Gene expression is governed by transcription factors (TFs) that commonly recognize short DNA sequence motifs. However, TF recruitment to genomic target sites in chromatin is complex and many parameters that ultimately dictate binding-site specificity are still unknown. Here, we systematically explore the interaction of TFs with synthetic and endogenous G-quadruplexes (G4s) DNA secondary structures. Our findings reveal that certain TFs are directly recruited to promoters by endogenous G4s with binding affinities comparable to canonical B-DNA binding and that endogenous G4-TF interactions can be disrupted with synthetic small molecule ligands. G4s in promoters are bound by a large number of TFs and associated with high transcriptional activity. This discovery of structure-specific recognition expands our understanding of how TFs regulate gene transcription.
2021-03-24 | GSE145090 | GEO
Project description:The identification of DNA G-quadruplexes (G4s) in the genome is important to study different biological processes in which these structures play a role, such as genome rearrangement, transcriptional regulation and DNA replication. G4-seq allowed the high-throughput experimental mapping of G-quadruplexes in the human genome. We developed here an improved version of this method, named G4-seq2, which we applied to generate G-quadruplexes genomic maps for 12 species, selected as important models organism to study development or as pathogens of clinical relevance. Those multi-species maps, publicly available for the community, will allow to further understand the design principle of G-quadruplex formation in genomic context, to study G-quadruplex biology in those model organisms, to predict ligand targeting for therapeutic usage and to design G-quadruplex computational predictors based on genome-wide experimental measurements.
2018-08-01 | GSE110582 | GEO
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:This SuperSeries is composed of the SubSeries listed below.
2025-08-06 | GSE221100 | GEO
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:Biallelic pathogenic variants in the essential DNA repair gene BRCA2 causes Fanconi anemia, complementation group FA-D1. Patients in this group are highly prone to develop embryonal tumors, most commonly medulloblastoma arising from the cerebellar granule cell progenitors (GCPs). GCPs undergo high proliferation in the postnatal cerebellum under SHH activation, but the type of DNA lesions that require the function of the BRCA2 to prevent tumorigenesis remains unknown. To identify such lesions, we assessed both GCP neurodevelopment and tumor formation using a mouse model with deletion of exons three and four of Brca2 in the central nervous system, coupled with global Trp53 loss. Brca2Δex3-4;Trp53-/- animals developed SHH subgroup medulloblastomas with complete penetrance. Whole-genome sequencing of the tumors identified structural variants with breakpoints enriched in areas overlapping G-quadruplexes (G4s). Brca2-deficient GCPs exhibited decreased replication speed in the presence of the G4-stabilizer pyridostatin. Pif1 helicase, which resolves G4s during replication, was highly upregulated in tumors, and Pif1 knockout in primary MB tumor cells resulted in increased genome instability upon pyridostatin treatment. These data suggest that G4s may represent sites prone to replication stalling in highly proliferative GCPs and without BRCA2, G4s become a source of genome instability. Tumor cells upregulate G4-resolving helicases to facilitate rapid proliferation through G4s highlighting PIF1 helicase as a potential therapeutic target for treatment of BRCA2-deficient medulloblastomas.
2025-08-05 | GSE288159 | GEO