G4access identifies G-quadruplexes and their associations with open chromatin and imprinting control regions

Esnault, Cyril; Magat, Talha; Zine El Aabidine, Amal; Garcia-Oliver, Encar; Cucchiarini, Anne; Bouchouika, Soumya; Lleres, David; Goerke, Lutz; Luo, Yu; Verga, Daniela; Lacroix, Laurent; Feil, Robert; Spicuglia, Salvatore; Mergny, Jean-Louis; Andrau, Jean-Christophe

doi:10.1038/s41588-023-01437-4

Cited by 21 publications

(13 citation statements)

References 61 publications

(72 reference statements)

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“…The presence of PQS was searched for detection thresholds above 1.2, 1.5, 1.8, and 2.0. PQS appearing at higher thresholds have a higher propensity to fold into G4s and form very stable structures . The raw data for all genomes analyzed are in Supporting Information 01, which also provides information on NCBI accession numbers, length, GC count, percentage GC genome content, and the number and frequency of PQS.…”

Section: Methodsmentioning

confidence: 99%

Abundance of G-Quadruplex Forming Sequences in the Hepatitis Delta Virus Genomes

Brázda,

Valková,

Dobrovolná

et al. 2024

ACS Omega

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Hepatitis delta virus (HDV) is a highly unusual RNA satellite virus that depends on the presence of hepatitis B virus (HBV) to be infectious. Its compact and variable single-stranded RNA genome consists of eight major genotypes distributed unevenly across different continents. The significance of noncanonical secondary structures such as G-quadruplexes (G4s) is increasingly recognized at the DNA and RNA levels, particularly for transcription, replication, and translation. G4s are formed from guanine-rich sequences and have been identified in the vast majority of viral, eukaryotic, and prokaryotic genomes. In this study, we analyzed the G4 propensity of HDV genomes by using G4Hunter. Unlike HBV, which has a G4 density similar to that of the human genome, HDV displays a significantly higher number of potential quadruplex-forming sequences (PQS), with a density more than four times greater than that of the human genome. This finding suggests a critical role for G4s in HDV, especially given that the PQS regions are conserved across HDV genotypes. Furthermore, the prevalence of G4-forming sequences may represent a promising target for therapeutic interventions to control HDV replication.

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Section: Methodsmentioning

confidence: 99%

Abundance of G-Quadruplex Forming Sequences in the Hepatitis Delta Virus Genomes

Brázda,

Valková,

Dobrovolná

et al. 2024

ACS Omega

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“…Further, since G4 has been shown to cooperate with transcription factors at gene promoters 27,28 , we analyzed publicly available NGS data that were generated implementing different methods for the assessment of G4 formation (Figure 2i). On one hand, we analyzed ChIP-seq data that were generated using an artificial 6.7 kDa G4 probe (G4P) protein, which binds G4s with high affinity and specificity 24 .…”

Section: Mir-9 Is Required For H3k4me3 Broad Domains High Basal Trans...mentioning

confidence: 99%

“…On one hand, we analyzed ChIP-seq data that were generated using an artificial 6.7 kDa G4 probe (G4P) protein, which binds G4s with high affinity and specificity 24 . On the other hand, we analyzed NGS data that were generated by G4access, which is an antibody-independent method that relies on moderate nuclease digestion of chromatinized DNA 28 . Remarkably, we found by both approaches enrichment of G4 at the TSS of the miR-9 target gene (Figure 2i).…”

Section: Mir-9 Is Required For H3k4me3 Broad Domains High Basal Trans...mentioning

confidence: 99%

“…A G4 is a stable nucleic acid secondary structure formed by square planes, in which four guanines located in the same plane stabilized by a monovalent cation 20,21 . While the early work about G4s mainly focused on their roles in telomeres 22 , recent studies demonstrated that G4s are both, enriched at promoters 23,24 and related to increased gene expression [25][26][27][28][29] . On the other hand, G4s were also located in gene bodies and related to reduced gene expression by inhibiting elongation of RNA polymerase 30,31 .…”

Section: Introductionmentioning

confidence: 99%

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3D genome organization during TGFB-induced transcription requires nuclear microRNA and G-quadruplexes

Cordero,

Swaminathan,

Rogel-Ayala

et al. 2023

Preprint

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Studying the dynamics of three-dimensional (3D) chromatin structure is essential to understand biological processes in the cell nucleus. Recent publications based on integrative analysis of multi-omics studies have provided comprehensive and multilevel insights into 3D genome organization emphasizing its role during transcriptional regulation. While enhancers are regulatory elements that play a central role in the spatiotemporal control of gene expression, chromatin looping has been broadly accepted as a means for enhancer-promoter interactions allowing them to stablish cell-type-specific gene expression signatures. On the other hand, G-quadruplexes (G4s) are non-canonical DNA secondary structures that are both, enriched at promoters and related to increased gene expression. However, the role of G4s in promoter-distal regulatory elements, such as super-enhancers (SE), as well as in 3D genome organization and chromatin looping mediating long-range enhancer-promoter interactions has remained elusive. Here we show that mature microRNA 9 (miR-9) is enriched at promoters and SE of genes that are inducible by tissue growth factor beta 1 (TGFB1) signaling. Further, we found that nuclearmiR-9is required for chromatin features related to increased transcriptional activity, such as broad domains of the euchromatin histone mark H3K4me3 (histone 3 tri-methylated lysine 4) and G4s. Moreover, we show that nuclearmiR-9is required for promoter-super-enhancer looping. Our study places a nuclear microRNA in the same structural and functional context with G4s and promoter-enhancer interactions during 3D genome organization and transcriptional activation induced by TGFB1 signaling, a critical regulator of proliferation programs in cancer and fibrosis.

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“…ComputaPonal studies have shown that G4s are not randomly distributed in the human genome; instead, they are concentrated in funcPonal regions such as promoters [9], telomeres [10], and intron-exon borders [11], suggesPng that G4s may have biological funcPons. Furthermore, in recent years, with the widespread applicaPon of single-molecule techniques in G4 research and the development of whole genome methods, including G4 ChIP-seq [12] and G4Access [13], more and more evidence indicates that G4s, parPcularly G4 secondary structures, are not genomic "junk" or accidents but possess important biological funcPons. Extensive studies have revealed that G4s are widely involved in the regulaPon of a variety of biological processes, including gene transcripPon [9], protein translaPon [14], genome stability [15], telomere regulaPon [16], and genome replicaPon [17].…”

Section: Introduc2onmentioning

confidence: 99%

G-quadruplexes as pivotal components ofcis-regulatory elements in the human genome

Zhang,

Wang,

Wang

et al. 2024

Preprint

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Cis-regulatory elements have the ability to precisely regulate gene expression in cells, and G-quadruplexes (G4s), as non-canonical secondary structures, may potentially play a role in this regulation. However, a lack of systematic studies exists to uncover the connection between these two elements. Here, we comprehensively characterized the associations between G4s and human candidatecis-regulatory elements (cCREs) inferred from the Encyclopedia of DNA Elements (ENCODE) data. Our findings demonstrate that G4s are prominently enriched in most types of cCREs, particularly in elements with promoter-like signatures (PLS). Furthermore, we observed that the co-occurrence of CTCF signals with H3K4me3 or H3K27ac signals significantly strengthens the association between cCREs and G4s. This association becomes more pronounced when examining cell type-specific cCREs and G4s. Interestingly, compared to cCREs, genetic variants occurring in G4s, especially within their G-runs, often exhibit higher regulatory potential and deleterious effects. Runs of several consecutive guanines (G-runs) in the vicinity of transcriptional start sites tend to be more constrained in mammalian evolution than cCREs’s G-runs. Besides, the presence of G4s, is often linked to a more favorable local chromatin environment for the activation and execution of regulatory functions of cCREs, potentially attributable to the formation of G4 secondary structures. Finally, we discovered that G4-associated cCREs exhibit widespread activation in a variety of cancers. Altogether, our study suggests that G4s are integral components of humancis-regulatory elements, and the G4 primary sequences are associated with the localization of the cCREs, while the G4 structures are linked to the activation of the cCREs. Therefore, we propose to define G4s as pivotal regulatory elements in the human genome.

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G4access identifies G-quadruplexes and their associations with open chromatin and imprinting control regions

Cited by 21 publications

References 61 publications

Abundance of G-Quadruplex Forming Sequences in the Hepatitis Delta Virus Genomes

Abundance of G-Quadruplex Forming Sequences in the Hepatitis Delta Virus Genomes

3D genome organization during TGFB-induced transcription requires nuclear microRNA and G-quadruplexes

G-quadruplexes as pivotal components ofcis-regulatory elements in the human genome

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