Evidence map›Paper›PMID 41688464›Full record

ArticleNature communications2026

ATRX loss couples genome instability at a G-rich repeat to dysregulation of human alpha-globin expression.

Yuqi Shen, Kinam Gupta, Sue Mei Tan-Wong, Sean Wen, Christopher A Fisher, Liezel Tamon, Nicholas J Proudfoot, Richard J Gibbons, Douglas R Higgs

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PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Yuqi ShenChinese Academy of Medical Sciences Oxford Institute (COI), Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0009-0008-9114-8743
Kinam GuptaLaboratory of Gene Regulation, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Sue Mei Tan-WongSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Sean WenMedical Research Council (MRC) Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Christopher A FisherMedical Research Council (MRC) Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Liezel TamonCentre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Nicholas J ProudfootSir William Dunn School of Pathology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-8646-3222
Richard J GibbonsChinese Academy of Medical Sciences Oxford Institute (COI), Nuffield Department of Medicine, University of Oxford, Oxford, UK. richard.gibbons@ndcls.ox.ac.uk.
Douglas R HiggsChinese Academy of Medical Sciences Oxford Institute (COI), Nuffield Department of Medicine, University of Oxford, Oxford, UK. doug.higgs@imm.ox.ac.uk.ORCID http://orcid.org/0000-0003-3579-8705

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Germline mutations in the chromatin remodelling protein ATRX cause a severe developmental disorder associated with α-thalassemia. In addition, ATRX is amongst the twenty genes most frequently mutated in cancer. How ATRX mutations alter gene expression remains unclear. Using the α-globin locus as a model, here we show that ATRX deficiency downregulates α-globin in a subset of cells exhibiting DNA damage. A G-rich repeat at the α-globin locus serves as a potential site of G-quadruplex formation and DNA damage. ATRX binds this repeat co-transcriptionally, and its loss increases R-loop accumulation at this site, leading to local DNA damage and transcriptional disruption in cis. Deletion of this repeat abolishes this effect, while targeted DNA damage reinstates it. These findings reveal a mechanism linking ATRX's role in genome stability to transcriptional regulation and uncover a molecular basis of human genetic disease mediated via a distal G-rich repeat.

Indexed as

alpha-GlobinsDNA HelicasesGenomic InstabilityNuclear ProteinsX-linked Nuclear Proteinalpha-ThalassemiaDNA DamageGene Expression RegulationG-QuadruplexesHumansR-Loop StructuresTranscription, Geneticalpha-GlobinsATRX protein, humanDNA HelicasesNuclear ProteinsX-linked Nuclear Protein

Identifiers

PMID41688464
PMCPMC13018553

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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.