ArticleThe EMBO journal2007
Embryonic and fetal beta-globin gene repression by the orphan nuclear receptors, TR2 and TR4.
Article in The EMBO journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04432623 (A Phase 1b Sequential Open Label Dose-Ranging Study of Safety, Pharmacokinetics, and Preliminary Activity of Benserazide in Subjects With Beta Thalassemia Intermedia and Sickle Cell Disease), which is not on this map. Cited by 68 papers.
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.
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.
A Phase 1b Sequential Open Label Dose-Ranging Study of Safety, Pharmacokinetics, and Preliminary Activity of Benserazide in Subjects With Beta Thalassemia Intermedia and Sickle Cell Disease
Who cites it
68 citing papers in PubMed, 96 citations in OpenAlex.
- Orphan Nuclear Receptors TR2 and TR4 in Erythropoiesis: From Mechanisms to Therapies.Biomolecules · 2025Review
- Article
- 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
- An Insight into the Role of GLIS1 in Embryonic Development, iPSC Generation, and Cancer.Advances in experimental medicine and biology · 2024Review
- Construction of a trio-based structural variation panel utilizing activated T lymphocytes and long-read sequencing technology.Communications biology · 2022Article
- Down-regulation of the transcriptional repressor ZNF802 (JAZF1) reactivates fetal hemoglobin in βScientific reports · 2022Article
- Role of Nuclear Receptors in Controlling Erythropoiesis.International journal of molecular sciences · 2022Review
- Article
- Transcriptional silencing of fetal hemoglobin expression by NonO.Nucleic acids research · 2021Article
- The Coup-TFII orphan nuclear receptor is an activator of the γ-globin gene.Haematologica · 2021Article
- Physiological and Aberrant γ-Globin Transcription During Development.Frontiers in cell and developmental biology · 2021Review
- Epigenetic Reexpression of Hemoglobin F Using Reversible LSD1 Inhibitors: Potential Therapies for Sickle Cell Disease.ACS omega · 2020Article
- Small molecule therapeutics to treat the β-globinopathies.Current opinion in hematology · 2020Review
- Article
- Dichotomy in redundant enhancers points to presence of initiators of gene regulation.BMC genomics · 2018Article
- BAP1 regulation of the key adaptor protein NCoR1 is critical for γ-globin gene repression.Genes & development · 2018Article
- Potential role of LSD1 inhibitors in the treatment of sickle cell disease: a review of preclinical animal model data.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Review
- Article
8 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
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The TR2 and TR4 orphan nuclear receptors comprise the DNA-binding core of direct repeat erythroid definitive, a protein complex that binds to direct repeat elements in the embryonic and fetal beta-type globin gene promoters. Silencing of both the embryonic and fetal beta-type globin genes is delayed in definitive erythroid cells of Tr2 and Tr4 null mutant mice, whereas in transgenic mice that express dominant-negative TR4 (dnTR4), human embryonic epsilon-globin is activated in primitive and definitive erythroid cells. In contrast, human fetal gamma-globin is activated by dnTR4 only in definitive, but not in primitive, erythroid cells, implicating TR2/TR4 as a stage-selective repressor. Forced expression of wild-type TR2 and TR4 leads to precocious repression of epsilon-globin, but in contrast to induction of gamma-globin in definitive erythroid cells. These temporally specific, gene-selective alterations in epsilon- and gamma-globin gene expression by gain and loss of TR2/TR4 function provide the first genetic evidence for a role for these nuclear receptors in sequential, gene-autonomous silencing of the epsilon- and gamma-globin genes during development, and suggest that their differential utilization controls stage-specific repression of the human epsilon- and gamma-globin genes.
Indexed as
Identifiers
What OpenQuestion holds
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.