ArticleBlood2015
Compound loss of function of nuclear receptors Tr2 and Tr4 leads to induction of murine embryonic β-type globin genes.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Orphan Nuclear Receptors TR2 and TR4 in Erythropoiesis: From Mechanisms to Therapies.Biomolecules · 2025Review
- Article
- Review
- 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
- Epigenetic effects toward new insights as potential therapeutic target in B-thalassemia.Journal, genetic engineering & biotechnology · 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 activities in erythroid cell gene regulation.Seminars in hematology · 2021Article
- Article
- BAP1 regulation of the key adaptor protein NCoR1 is critical for γ-globin gene repression.Genes & development · 2018Article
- Mouse Models of Erythropoiesis and Associated Diseases.Methods in molecular biology (Clifton, N.J.) · 2018Review
- Article
- Fetal hemoglobin in sickle cell anemia: The Arab-Indian haplotype and new therapeutic agents.American journal of hematology · 2017Review
- Heterochromatin Protein 1γ Is a Novel Epigenetic Repressor of Human Embryonic ϵ-Globin Gene Expression.The Journal of biological chemistry · 2017Article
- ε-globin expression is regulated by SUV4-20h1.Haematologica · 2016Article
- Article
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 3 institutions in 3 countries.
Funding
Abstract
The orphan nuclear receptors TR2 and TR4 have been shown to play key roles in repressing the embryonic and fetal globin genes in erythroid cells. However, combined germline inactivation of Tr2 and Tr4 leads to periimplantation lethal demise in inbred mice. Hence, we have previously been unable to examine the consequences of their dual loss of function in adult definitive erythroid cells. To circumvent this issue, we generated conditional null mutants in both genes and performed gene inactivation in vitro in adult bone marrow cells. Compound Tr2/Tr4 loss of function led to induced expression of the embryonic εy and βh1 globins (murine counterparts of the human ε- and γ-globin genes). Additionally, TR2/TR4 function is required for terminal erythroid cell maturation. Loss of TR2/TR4 abolished their occupancy on the εy and βh1 gene promoters, and concurrently impaired co-occupancy by interacting corepressors. These data strongly support the hypothesis that the TR2/TR4 core complex is an adult stage-specific, gene-selective repressor of the embryonic globin genes. Detailed mechanistic understanding of the roles of TR2/TR4 and their cofactors in embryonic and fetal globin gene repression may ultimately enhance the discovery of novel therapeutic agents that can effectively inhibit their transcriptional activity and be safely applied to the treatment of β-globinopathies.
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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.