Evidence map›Paper›PMID 40468392›Full record

ArticleGenome biology2025

DNA G-quadruplex structures act as functional elements in α- and β-globin enhancers.

Colm Doyle, Krzysztof Herka, Sean M Flynn, Larry Melidis, Somdutta Dhir, Stefan Schoenfelder, David Tannahill, Shankar Balasubramanian

Abstract read
In one paragraph

Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Review
  2. G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  3. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Colm Doyle *Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Krzysztof Herka *Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Sean M Flynn *Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Larry MelidisCancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Somdutta DhirCancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Stefan SchoenfelderEpigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK.
David TannahillCancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Shankar BalasubramanianCancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. sb10031@cam.ac.uk.

Funding

Babraham Institute BBS/E/B/000C0421Cancer Research UK C9545/A19863Leverhulme Trust ECF-2021-398UK Research and Innovation MR/T016787/1Wellcome TrustWellcome Trust 209441/Z/17/Z
6 · The paper itself

Abstract

backgroundEnhancer elements interact with target genes at a distance to modulate their expression, but the molecular details of enhancer-promoter interaction are incompletely understood. G-quadruplex DNA secondary structures (G4s) have recently been shown to co-occur with 3D chromatin interactions; however, the functional importance of G4s within enhancers remains unclear.

resultsIn this study, we identify novel G4 structures within two locus control regions at the human α- and β-globin loci. We find that mutating G4 motifs by genome editing prevents their folding into G4 structures in cells and disrupts 3D enhancer-promoter interactions and target gene expression in a manner comparable to whole enhancer deletion. Furthermore, restoration of G4 structure formation using a dissimilar G4-forming primary sequence recovers specific enhancer-gene interactions and gene expression. Through proteomic, biophysical, and genomic profiling, we find that enhancer G4s are tightly linked to the maintenance of an active chromatin state and RNA polymerase II recruitment to regulate target gene expression.

conclusionsOur study shows that folded G4 structures can act as functional elements that mediate 3D enhancer-promoter interactions to support enhancer-driven globin gene regulation.

Indexed as

alpha-Globinsbeta-GlobinsEnhancer Elements, GeneticG-QuadruplexesChromatinGene Expression RegulationHumansPromoter Regions, Geneticalpha-Globinsbeta-GlobinsChromatin3D chromatin interactionsEnhancersEpigeneticsG-quadruplex structures

Identifiers

PMID40468392
PMCPMC12139101

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.