Evidence map›Paper›PMID 40637230›Full record

ArticleNucleic acids research2025

Dissecting the epigenetic regulation of the fetal hemoglobin genes to unravel a novel therapeutic approach for β-hemoglobinopathies.

Simone Amistadi, Letizia Fontana, Chiara Magnoni, Tristan Felix, Matteo Kane Charvin, Pierre Martinucci, Candice Gautier, Lilian Greau, Bettina Bessières, Panagiotis Antoniou and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Dissecting polycomb complexes for enhanced fetal hemoglobin production.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Review
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

14 authors.

Simone AmistadiLaboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR1163, Paris Cité University, Paris, 75015, France.
Letizia FontanaLaboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR1163, Paris Cité University, Paris, 75015, France.
Chiara MagnoniLaboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR1163, Paris Cité University, Paris, 75015, France.ORCID 0009-0007-9252-9321
Tristan FelixLaboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR1163, Paris Cité University, Paris, 75015, France.
Matteo Kane CharvinLaboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR1163, Paris Cité University, Paris, 75015, France.
Pierre MartinucciLaboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR1163, Paris Cité University, Paris, 75015, France.
Candice GautierLaboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Imagine Institute, INSERM UMR1163, Paris, 75015, France.
Lilian GreauGenomics Core Facility, Institut Imagine-Structure Fédérative de Recherche Necker, INSERM U1163 et INSERM US24/CNRS UAR3633, Paris Cité University, Paris, 75015, France.
Bettina BessièresService de Médecine Génomique des Maladies Rares, Hôpital Necker-Enfants Malades, Paris, 75015, France.
Panagiotis AntoniouLaboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR1163, Paris Cité University, Paris, 75015, France.
Oriana RomanoDepartment of Molecular Medicine, University of Padova, Padova, 35122, Italy.
Eric AllemandLaboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Imagine Institute, INSERM UMR1163, Paris, 75015, France.
Claudio MussolinoInstitute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, 79098, Freiburg, Germany.ORCID 0000-0003-2073-1110
Annarita MiccioLaboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR1163, Paris Cité University, Paris, 75015, France.ORCID 0000-0002-3409-9665

Funding

Agence Nationale de la Recherches ANR-10-IAHU-01Agence Nationale de la Recherches ANR-21-CE18-0066-01European Cooperation in Science and Technology CA21113Fondation pour la Recherche Médicale PLP202110014595French National Research AgencyInstitut Imagine
6 · The paper itself

Abstract

Beta-hemoglobinopathies are severe genetic diseases caused by mutations affecting the production of the adult β-globin chain. The clinical severity is mitigated by the co-inheritance of mutations that reactivate the production of the fetal β-like γ-globin in adults. However, the epigenetic mechanisms underlying the adult-to-fetal hemoglobin (HbA-to-HbF) switching are still not fully understood. Here, we used epigenome editing technologies to dissect the molecular mechanisms underlying γ- and β-globin gene regulation and to develop novel potential therapeutics for β-hemoglobinopathies. Targeted removal of DNA methylation by dCas9-Tet1 (alone or together with the deposition of histone acetylation by CBP-dCas9) at the fetal promoters led to efficient and durable γ-globin reactivation, demonstrating that DNA methylation is a driver for HbF repression. This strategy, characterized by high specificity and a good safety profile, led to a substantial correction of the pathological phenotype in erythroid cells from patients with sickle cell disease.

Indexed as

Anemia, Sickle Cellbeta-GlobinsEpigenesis, GeneticFetal HemoglobinHemoglobinopathiesCRISPR-Cas SystemsDNA MethylationErythroid Cellsgamma-GlobinsGene EditingHumansPromoter Regions, Geneticbeta-GlobinsFetal Hemoglobingamma-Globins

Identifiers

PMID40637230
PMCPMC12242770

What OpenQuestion holds

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Registered trials

None linked

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.