ArticleThe EMBO journal2002
An embryonic/fetal beta-type globin gene repressor contains a nuclear receptor TR2/TR4 heterodimer.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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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.
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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.
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Who cites it
75 citing papers in PubMed, 114 citations in OpenAlex.
- Systematic Review of Non-Coding Genomic Variants in Globin and Non-Globin Clusters and Their Impact on Phenotypic Severity in Thalassemia and Sickle Cell Disease.Journal of clinical medicine · 2026Review
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- Orphan Nuclear Receptors TR2 and TR4 in Erythropoiesis: From Mechanisms to Therapies.Biomolecules · 2025Review
- Article
- Genetic Modifiers of Hemoglobin Expression from a Clinical Perspective in Hemoglobinopathy Patients with Beta Thalassemia and Sickle Cell Disease.International journal of molecular sciences · 2024Review
- Exploring Novel Strategies to Alleviate Symptoms of β-Globinopathies: Examining the Potential Role of Embryonic ε-globin Induction.Transfusion medicine reviews · 2024Review
- PGC-1α agonism induces fetal hemoglobin and exerts antisickling effects in sickle cell disease.Science advances · 2024Article
- Spatiotemporal expression and control of haemoglobin in space.Nature communications · 2024Article
- Review
- An Insight into the Role of GLIS1 in Embryonic Development, iPSC Generation, and Cancer.Advances in experimental medicine and biology · 2024Review
- Combinatorial targeting of epigenome-modifying enzymes with decitabine and RN-1 synergistically increases HbF.Blood advances · 2023Article
- Effect of the LSD1 inhibitor RN-1 on γ-globin and global gene expression during erythroid differentiation in baboons (Papio anubis).PloS one · 2023Article
- Dual function NFI factors control fetal hemoglobin silencing in adult erythroid cells.Nature genetics · 2022Article
- Role of Nuclear Receptors in Controlling Erythropoiesis.International journal of molecular sciences · 2022Review
- Article
- Epigenetic activities in erythroid cell gene regulation.Seminars in hematology · 2021Article
- Physiological and Aberrant γ-Globin Transcription During Development.Frontiers in cell and developmental biology · 2021Review
- Small molecule therapeutics to treat the β-globinopathies.Current opinion in hematology · 2020Review
- Targeting sickle cell disease root-cause pathophysiology with small molecules.Haematologica · 2019Review
- Epsilon-Globin HBE1 Enhances Radiotherapy Resistance by Down-Regulating BCL11A in Colorectal Cancer Cells.Cancers · 2019Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We recently described an erythroid epsilon-globin gene repressor activity, which we named DRED (direct repeat erythroid-definitive). We show that DRED binds with high affinity to DR1 sites in the human embryonic (epsilon-) and fetal (gamma-) globin gene promoters, but the adult beta-globin promoter has no DR1 element. DRED is a 540 kDa complex; sequence determination showed that it contains the nuclear orphan receptors TR2 and TR4. TR2 and TR4 form a heterodimer that binds to the epsilon and gamma promoter DR1 sites. One mutation in a DR1 site causes elevated gamma-globin transcription in human HPFH (hereditary persistence of fetal hemoglobin) syndrome, and we show that this mutation reduces TR2/TR4 binding in vitro. The two receptor mRNAs are expressed at all stages of murine and human erythropoiesis; their forced transgenic expression reduces endogenous embryonic epsilony-globin transcription. These data suggest that TR2/TR4 forms the core of a larger DRED complex that represses embryonic and fetal globin transcription in definitive erythroid cells, and therefore that inhibition of its activity might be an attractive intervention point for treating sickle cell anemia.
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Registered trials
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.