Dimeric G-quadruplex motifs-induced NFRs determine strong replication origins in vertebrates
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA966151 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24982411_1.fastq.gz | Fastqsanger.gz | |||
| SRR24982411_2.fastq.gz | Fastqsanger.gz | |||
| SRR24982412_1.fastq.gz | Fastqsanger.gz | |||
| SRR24982412_2.fastq.gz | Fastqsanger.gz | |||
| SRR24982413_1.fastq.gz | Fastqsanger.gz |
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Project description:Replication of vertebrate genomes is tightly regulated to ensure accurate duplication, but our understanding of the interplay between genetic and epigenetic factors in this regulation remains incomplete. Here, we investigated the involvement of three elements enriched at gene promoters and replication origins: guanine-rich motifs potentially forming G-quadruplexes (pG4s), nucleosome-free regions (NFRs), and the histone variant H2A.Z, in the firing of origins of replication in vertebrates. We show that two pG4s on the same DNA strand (dimeric pG4s) are sufficient to induce assembly of an efficient minimal replication origin without inducing transcription. Dimeric pG4s in replication origins trigger formation of an NFR next to precisely positioned nucleosomes enriched in H2A.Z on this minimal origin and genome-wide. Thus, our data suggest a crucial role for dimeric pG4s in the organization and duplication of vertebrate genomes. It supports the hypothesis that a nucleosome close to an NFR is a shared signal for the formation of replication origins in eukaryotes.
2023-07-19 | GSE231492 | GEO
Project description:Replication of vertebrate genomes is tightly regulated to ensure accurate duplication, but our understanding of the interplay between genetic and epigenetic factors in this regulation remains incomplete. Here, we investigated the involvement of three elements enriched at gene promoters and replication origins: guanine-rich motifs potentially forming G-quadruplexes (pG4s), nucleosome-free regions (NFRs), and the histone variant H2A.Z, in the firing of origins of replication in vertebrates. We show that two pG4s on the same DNA strand (dimeric pG4s) are sufficient to induce the assembly of an efficient minimal replication origin without inducing transcription in avian DT40 cells. Dimeric pG4s in replication origins are associated with formation of an NFR next to precisely-positioned nucleosomes enriched in H2A.Z on this minimal origin and genome-wide. Thus, our data suggest that dimeric pG4s are important for the organization and duplication of vertebrate genomes. It supports the hypothesis that a nucleosome close to an NFR is a shared signal for the formation of replication origins in eukaryotes.
| S-EPMC10415359 | biostudies-literature
Project description:G-quadruplex structures in the 5’ UTR of mRNAs are widely considered to suppress translation without affecting transcription. The current study describes the comprehensive analysis of proteins binding to four different G-quadruplex motifs located in mRNAs of the cancer-related genes Bcl-2, NRAS, MMP16, and ARPC2. Following metabolic labeling (Stable Isotope Labeling with Amino acids in Cell culture, SILAC) of proteins in the human cell line HEK293, G-quadruplex binding proteins were enriched by pull-down assays and identified by LC-orbitrap mass spectrometry. We found different patterns of interactions for the G-quadruplex motifs under investigation. While the G-quadruplexes in the mRNAs of NRAS and MMP16 specifically interacted with a small number of proteins, the Bcl-2 and ARPC2 G-quadruplexes exhibited a broad range of proteinaceous interaction partners with 99 and 82 candidate proteins identified in at least two replicates, respectively. Among the interaction partners were many proteins known to bind to RNA, including multiple heterogenous nuclear ribonucleoproteins (hnRNPs). The identified ribosomal proteins are likely to reflect stalling of the ribosome by RNA G-quadruplex structures. In addition, several proteins were identified that have not previously been described to interact with RNA. Gene ontology analysis of the set of candidate proteins revealed that many interaction partners are known to be tumor related. The majority of the identified RNA G-quadruplex interacting proteins are thought to be involved in post-transcriptional processes, particularly in splicing. These findings indicate that protein-G-quadruplex interactions may be relevant to the regulation of mRNA maturation and may play an important role in tumor biology.
2017-11-14 | PXD005761 | Pride
Project description:RG/RGG boxes are common binding motifs in RNA-G-quadruplex-interacting proteins
| PRJNA417119 | ENA
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:The effect of bisquinolinium compounds PhenDC3 and 360A genome wide gene expression changes modulated via promoter based G-quadruplex (G4) motifs.
2012-05-30 | GSE32170 | 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: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:It is generally thought that splicing factors regulate alternative splicing through binding to RNA consensus sequences. In addition to these linear motifs, RNA secondary structure is emerging as an important layer in splicing regulation. Here we demonstrate that RNA elements with G-quadruplex forming capacity promote exon inclusion. Destroying G-quadruplex forming capacity while keeping G-tracts intact abrogates exon inclusion. Analysis of RNA binding protein footprints revealed that G-quadruplexes are enriched in hnRNPF-binding sites and near hnRNPF-regulated alternatively spliced exons in the human transcriptome. Moreover, hnRNPF regulates an EMT-associated CD44 isoform switch in a G-quadruplex-dependent manner, which results in inhibition of EMT. Mining breast cancer TCGA datasets, we demonstrate that hnRNPF negatively correlates with an EMT gene signature and positively correlates with patient survival. These data suggest a critical role for RNA G-quadruplexes in regulating alternative splicing. Modulation of G-quadruplex structural integrity may control cellular processes important for tumor progression.
2018-01-22 | GSE107542 | GEO
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