DNA G-quadruplex structures: more than simple roadblocks to transcription?

Robinson, Jenna; Raguseo, Federica; Nuccio, Sabrina Pia; Liano, Denise; Antonio, Marco Di

doi:10.1093/nar/gkab609

Cited by 203 publications

(158 citation statements)

References 101 publications

Supporting

Mentioning

142

Contrasting

Order By: Relevance

“…The conformation of G-quadruplex structures is dependent on loop length and loop sequence composition ( 6 ): Four GGG-repeats connected by short loops on the same DNA molecule form the canonical intramolecular G4, but G4s have also been shown to fold with longer loops, as few as two or more than three guanine quartets, or with non-G bases breaking up the consecutive G-repeat. Further, GGG-repeats distributed on both strands of a DNA duplex can form inter-strand G4s, and it has been proposed that inter-strand G4s may also form across longer distances via DNA looping ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide mapping of G-quadruplex structures with CUT&Tag

Lyu

Shao

Yung

et al. 2021

Nucleic Acids Research

119

View full text Add to dashboard Cite

Single-stranded genomic DNA can fold into G-quadruplex (G4) structures or form DNA:RNA hybrids (R loops). Recent evidence suggests that such non-canonical DNA structures affect gene expression, DNA methylation, replication fork progression and genome stability. When and how G4 structures form and are resolved remains unclear. Here we report the use of Cleavage Under Targets and Tagmentation (CUT&Tag) for mapping native G4 in mammalian cell lines at high resolution and low background. Mild native conditions used for the procedure retain more G4 structures and provide a higher signal-to-noise ratio than ChIP-based methods. We determine the G4 landscape of mouse embryonic stem cells (ESC), observing widespread G4 formation at active promoters, active and poised enhancers. We discover that the presence of G4 motifs and G4 structures distinguishes active and primed enhancers in mouse ESCs. Upon differentiation to neural progenitor cells (NPC), enhancer G4s are lost. Further, performing R-loop CUT&Tag, we demonstrate the genome-wide co-occurrence of single-stranded DNA, G4s and R loops at promoters and enhancers. We confirm that G4 structures exist independent of ongoing transcription, suggesting an intricate relationship between transcription and non-canonical DNA structures.

show abstract

Section: Introductionmentioning

confidence: 99%

Genome-wide mapping of G-quadruplex structures with CUT&Tag

Lyu

Shao

Yung

et al. 2021

Nucleic Acids Research

119

View full text Add to dashboard Cite

show abstract

“…Sequences that have the capacity to adopt alternative DNA secondary structures have been implicated in numerous heredity diseases and cancer 45, 61–66 . The presence of long structure-forming repeats can inhibit DNA replication 67–70 , repress transcription 56, 71, 72 , and promote genome instability 31, 65, 66, 73 . For example, highly expanded (TA)n repeats found in cancers with MSI are susceptible to replication fork stalling, collapse and chromosomal deletions 31 .…”

Section: Discussionmentioning

confidence: 99%

Linking Dynamic DNA Secondary Structures to Genome Instability

Nussenzweig¹,

Matos-Rodrigues²,

Wietmarschen

et al. 2022

Preprint

View full text Add to dashboard Cite

Genomic double-stranded DNA (dsDNA) becomes single-stranded (ssDNA) during replication, transcription, and DNA repair. ssDNA is therefore believed to be transient, occurring in only a fraction of the genome at a given time, and variable amongst a population of cells. These transiently formed ssDNA segments can also adopt alternative, dynamic DNA conformations, such as cruciform DNA, triplexes, quadruplexes and others. To determine whether there are stable and conserved regions of ssDNA, we utilized our previously developed method S1-END-seq to convert ssDNA to DNA double strand breaks (DSBs), which are then processed for high-throughput sequencing. This approach revealed two predominant dynamic DNA structures: cruciform DNA formed by expanded (TA)n repeats that accumulated uniquely in microsatellite unstable human cancer cell lines, and DNA triplexes (H-DNA) formed by homopurine/homopyrimidine mirror repeats common across a variety of human cell lines. Triplex-forming repeats accumulated during replication, blocked DNA synthesis and were hotspots of somatic mutation. In contrast, pathologically expanded repeats in Friedreichs ataxia patient cells formed a replication-independent and transcription-inducible DNA secondary structure. Our results identify dynamic DNA secondary structures in vivo that contribute to elevated genome instability.

show abstract

“…In this review we focus our attention largely on G4 DNA structures and the evidence for impact of methylated cytosine in modifying formation of these structures, and to a lesser extent consider impacts of methylation on i -motif and H-DNA/triplex DNA structures. G4 structures have been recognised for many decades, and the study of their in vivo properties is now an important area of genetic research [ 6 , 7 ]. Emerging bodies of evidence are describing the role that G4s contribute to genomic processes relevant to gene maintenance, regulation, and DNA replication.…”

Section: Introductionmentioning

confidence: 99%

The Dynamic Regulation of G-Quadruplex DNA Structures by Cytosine Methylation

Stevens

Jong

Kennedy

2022

IJMS

View full text Add to dashboard Cite

It is well known that certain non B-DNA structures, including G-quadruplexes, are key elements that can regulate gene expression. Here, we explore the theory that DNA modifications, such as methylation of cytosine, could act as a dynamic switch by promoting or alleviating the structural formation of G-quadruplex structures in DNA or RNA. The interaction between epigenetic DNA modifications, G4 formation, and the 3D architecture of the genome is a complex and developing area of research. Although there is growing evidence for such interactions, a great deal still remains to be discovered. In vivo, the potential effect that cytosine methylation may have on the formation of DNA structures has remained largely unresearched, despite this being a potential mechanism through which epigenetic factors could regulate gene activity. Such interactions could represent novel mechanisms for important biological functions, including altering nucleosome positioning or regulation of gene expression. Furthermore, promotion of strand-specific G-quadruplex formation in differentially methylated genes could have a dynamic role in directing X-inactivation or the control of imprinting, and would be a worthwhile focus for future research.

show abstract

DNA G-quadruplex structures: more than simple roadblocks to transcription?

Cited by 203 publications

References 101 publications

Genome-wide mapping of G-quadruplex structures with CUT&Tag

Genome-wide mapping of G-quadruplex structures with CUT&Tag

Linking Dynamic DNA Secondary Structures to Genome Instability

The Dynamic Regulation of G-Quadruplex DNA Structures by Cytosine Methylation

Contact Info

Product

Resources

About